oru.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1 - 37 av 37
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Borg, O. Anders
    et al.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Durbeej, Bo
    Electron-transfer induced repair of 6-4 photoproducts in DNA: a computational study.2007Ingår i: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 111, nr 12, s. 2351-2361Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mechanism employed by DNA photolyase to repair 6-4 photoproducts in UV-damaged DNA is explored by means of quantum chemical calculations. Considering the repair of both oxetane and azetidine lesions, it is demonstrated that reduction as well as oxidation enables a reversion reaction by creating anionic or cationic radicals that readily fragment into monomeric pyrimidines. However, on the basis of calculated reaction energies indicating that electron transfer from the enzyme to the lesion is a much more favorable process than electron transfer in the opposite direction, it is suggested that the photoenzymic repair can only occur by way of an anionic mechanism. Furthermore, it is shown that reduction of the oxetane facilitates a mechanism involving cleavage of the C−O bond followed by cleavage of the C−C bond, whereas reductive fragmentation of the azetidine may proceed with either of the intermonomeric C−N and C−C bonds cleaved as the first step. From calculations on neutral azetidine radicals, a significant increase in the free-energy barrier for the initial fragmentation step upon protonation of the carbonylic oxygens is predicted. This effect can be attributed to protonation serving to stabilize reactant complexes more than transition structures.

  • 2.
    Brumboiu, Iulia Emilia
    et al.
    Department of Theoretical Chemistry and Biology, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
    Eriksson, Olle
    Örebro universitet, Institutionen för naturvetenskap och teknik. Department of Physics and Astronomy, Uppsala University, Uppsala, Sweden.
    Norman, Patrick
    Department of Theoretical Chemistry and Biology, KTH Royal Institute of Technology, Stockholm, Sweden.
    Photoelectron Spectroscopy of Molecules Beyond the Electric Dipole Approximation2019Ingår i: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 15, nr 10, s. 5483-5494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A methodology implemented to compute photoionization cross sections beyond the electric dipole approximation using Gaussian type orbitals for the initial state and plane waves for the final state is applied to molecules of various sizes. The molecular photoionization cross sections computed for valence molecular orbitals as a function of photon energy present oscillations due to the wave-like nature of both the outgoing photoelectron and of the incoming photon. These oscillations are damped by rotational and vibrational averaging or by performing a k-point summation for the solid state case. For core orbitals, the corrections introduced by going beyond the electric dipole approximation are comparable to the atomic case. For valence orbitals, nondipole corrections to the total photoinization cross sections can reach up to 20% at photon energies above 1 keV. The corrections to the differential cross sections calculated at the magic angle are larger, reaching values between 30% and 50% for all molecules included. Our findings demonstrate that photoelectron spectroscopy, especially angle-resolved, on, e.g., molecules and clusters on surfaces, using high photon energies, must be accompanied by theories that go beyond the electric dipole approximation.

  • 3. Bunta, Juraj
    et al.
    Dahlberg, Martin
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Korolev, Nikolai
    Laaksonen, Aatto
    Lohikoski, Raimo
    Lyubartsev, Alexander
    Pinak, Miroslav
    Schyman, Patric
    Solvating, manipulating, damaging, and repairing DNA in a computer2007Ingår i: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 107, nr 2, s. 279-291Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This work highlights four different topics in modeling of DNA: (i) the importance of water and ions together with the structure and function of DNA; the hydration structure around the ions appears to be the determining factor in the ion coordination to DNA, as demonstrated in the results of our MD simulations; (ii) how MD simulations can be used to simulate single molecule manipulation experiments as a complement to reveal the structural dynamics of the studied biomolecules; (iii) how damaged DNA can be studied in computer simulations; and (iv) how repair of damaged DNA can be studied theoretically.

  • 4.
    Bushnell, Eric A C
    et al.
    University of Windsor, Windsor, ON, N9B 3P4, Canada.
    Erdtman, Edvin
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Llano, Jorge
    University of Windsor, Windsor, ON, N9B 3P4, Canada.
    Eriksson, Leif A.
    National University of Ireland, Galway, University Road, Galway, Ireland.
    Gauld, James W.
    University of Windsor, Windsor, ON, N9B 3P4, Canada.
    Computational insights into the first branching point in porphyrin biosynthesis: decarboxylation of ring D in URO–III by Uroporphyrinogen–III DecarboxylaseManuskript (preprint) (Övrigt vetenskapligt)
  • 5.
    Bushnell, Eric A. C.
    et al.
    Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada.
    Erdtman, Edvin
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Llano, Jorge
    Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada.
    Eriksson, Leif A.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Gauld, James W.
    Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada.
    The first branching point in porphyrin biosynthesis: a systematic docking, molecular dynamics and quantum mechanical/molecular mechanical study of substrate binding and mechanism of uroporphyrinogen-III decarboxylase2011Ingår i: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 32, nr 5, s. 822-834Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In humans, uroporphyrinogen decarboxylase is intimately involved in the synthesis of heme, where the decarboxylation of the uroporphyrinogen-III occurs in a single catalytic site. Several variants of the mechanistic proposal exist; however, the exact mechanism is still debated. Thus, using an ONIOM quantum mechanical/molecular mechanical approach, the mechanism by which uroporphyrinogen decarboxylase decarboxylates ring D of uroporphyrinogen-III has been investigated. From the study performed, it was found that both Arg37 and Arg50 are essential in the decarboxylation of ring D, where experimentally both have been shown to be critical to the catalytic behavior of the enzyme. Overall, the reaction was found to have a barrier of 10.3 kcal mol−1 at 298.15 K. The rate-limiting step was found to be the initial protontransfer from Arg37 to the substrate before the decarboxylation. In addition, it has been found that several key interactions exist between the substrate carboxylate groups and backbone amides of various activesite residues as well as several other functional groups.

  • 6.
    Erdtman, Edvin
    Örebro universitet, Akademin för naturvetenskap och teknik.
    5-Aminolevulinic acid and derivatives thereof: properties, lipid permeability and enzymatic reactions2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    5-aminolevulinic acid (5-ALA) and derivatives thereof are widely usedprodrugs in treatment of pre-malignant skin diseases of the cancer treatmentmethod photodynamic therapy (PDT). The target molecule in 5-ALAPDTis protoporphyrin IX (PpIX), which is synthesized endogenously from5-ALA via the heme pathway in the cell. This thesis is focused on 5-ALA,which is studied in different perspectives and with a variety of computationalmethods. The structural and energetic properties of 5-ALA, itsmethyl-, ethyl- and hexyl esters, four different 5-ALA enols, and hydrated5-ALA have been investigated using Quantum Mechanical (QM) first principlesdensity functional theory (DFT) calculations. 5-ALA is found to bemore stable than its isomers and the hydrolysations of the esters are morespontaneous for longer 5-ALA ester chains than shorter. The keto-enoltautomerization mechanism of 5-ALA has been studied, and a self-catalysismechanism has been proposed to be the most probable. Molecular Dynamics(MD) simulations of a lipid bilayer have been performed to study themembrane permeability of 5-ALA and its esters. The methyl ester of 5-ALAwas found to have the highest permeability constant (PMe-5-ALA = 52.8 cm/s).The mechanism of the two heme pathway enzymes; Porphobilinogen synthase(PBGS) and Uroporphyrinogen III decarboxylase (UROD), have beenstudied by DFT calculations and QM/MM methodology. The rate-limitingstep is found to have a barrier of 19.4 kcal/mol for PBGS and 13.7kcal/mol for the first decarboxylation step in UROD. Generally, the resultsare in good agreement with experimental results available to date.

    Delarbeten
    1. Theoretical study of 5-aminolevulinic acid (5ALA) and some pharmaceutically important derivatives
    Öppna denna publikation i ny flik eller fönster >>Theoretical study of 5-aminolevulinic acid (5ALA) and some pharmaceutically important derivatives
    2007 (Engelska)Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 434, nr 1-3, s. 101-106Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    5-Aminolevulinic acid (5ALA) is the key synthetic building block in protoporphyrin IX (PpIX), the heme chromophore in mitochondria. The addition of extracorporeal 5ALA and its alkyl ester derivatives are in current clinical use in photodynamical diagnostics and photodynamic therapy of tumors and skin disorders. In the current study density functional theory calculations are performed on 5ALA and its methyl, ethyl, and hexyl esters, in order to explore the basic chemical properties of these species. It is concluded that even in aqueous media the zwitterionic form of 5ALA is less stable than the non-zwitterionic one, that the local environment (lipid vs water) affects the energetics of reaction considerably, and that the hexyl species is most prone to hydrolysis of the three alkyl ester derivatives.

    Ort, förlag, år, upplaga, sidor
    Amsterdam: North-Holland Publishing Co, 2007
    Nyckelord
    5-aminolevulinic acid, 5ALA, B3LYP, DFT, Protonation states, Alkyl esters
    Nationell ämneskategori
    Teoretisk kemi Fysikalisk kemi
    Forskningsämne
    Biokemi; Fysikalisk kemi
    Identifikatorer
    urn:nbn:se:oru:diva-4092 (URN)10.1016/j.cplett.2006.11.084 (DOI)000243820100020 ()2-s2.0-33846018089 (Scopus ID)
    Tillgänglig från: 2007-06-25 Skapad: 2007-06-25 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
    2. Theoretical study of 5-aminolevulinic acid tautomerization: a novel self-catalyzed mechanism
    Öppna denna publikation i ny flik eller fönster >>Theoretical study of 5-aminolevulinic acid tautomerization: a novel self-catalyzed mechanism
    2008 (Engelska)Ingår i: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 112, nr 18, s. 4367-4374Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    5-Aminolevulinic acid (5ALA) is the key synthetic building block in protoporphyrin IX (PpIX), the heme chromophore in mitochondria. In this study density functional theory calculations were performed on the tautomers of 5ALA and the tautomerization reaction mechanism from its enolic forms (5-amino-4-hydroxypent-3-enoic acid and 5-amino-4-hydroxypent-4-enoic acid) to the more stable 5ALA. The hydrated form 5-amino-4,4-dihydroxypentanoic acid was also studied. The lowest energy pathway of 5ALA tautomerization is by means of autocatalysis, in that an oxygen of the carboxylic group transfers the hydrogen atom as a "crane", with an activation energy of similar to 15 kcal/mol. This should be compared to the barriers of about 35 kcal/mol for water assisted tautomerization, and 60 kcal/mol for direct hydrogen transfer. For hydration of 5ALA, the water catalyzed activation barrier is found to be similar to 35 kcal/mol, approximately 5 kcal/mol lower than direct hydration.

    Ort, förlag, år, upplaga, sidor
    Washington DC: American Chemical Society, 2008
    Nyckelord
    Aminolevulinic Acid/*chemistry, Carboxylic Acids/chemistry, Catalysis, Isomerism, Protons, Quantum Theory, Thermodynamics, Water/chemistry
    Nationell ämneskategori
    Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Fysikalisk kemi Teoretisk kemi
    Forskningsämne
    Biokemi; Fysikalisk kemi
    Identifikatorer
    urn:nbn:se:oru:diva-4625 (URN)10.1021/jp7118197 (DOI)000255486400026 ()18416542 (PubMedID)2-s2.0-43949116597 (Scopus ID)
    Tillgänglig från: 2008-10-13 Skapad: 2008-10-13 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
    3. Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer
    Öppna denna publikation i ny flik eller fönster >>Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer
    2008 (Engelska)Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 463, nr 1-3, s. 178-182Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    5-Aminolevulinic acid (5ALA) and ester derivates thereof are used as prodrugs in photodynamic therapy (PDT). The behavior of 5ALA and three esters of 5ALA in a DPPC lipid bilayer is investigated. In particular, the methyl ester displays a very different free energy profile, where the highest barrier is located in the region with highest lipid density, while the others have their peak in the middle of the membrane, and also displays a considerably lower permeability coefficient than neutral 5ALA and the ethyl ester. The zwitterion of 5ALA has the highest permeability constant, but a significant free energy minimum in the polar head-group region renders an accumulation in this region.

    Ort, förlag, år, upplaga, sidor
    Amsterdam: North-Holland Publishing Co, 2008
    Nyckelord
    Molecular-dynamics simulations, photodynamic therapy, adenocarcinoma cells, beta transporters, hydrated DPPC, derivates, permeation, protoporphyrin, transition, membranes
    Nationell ämneskategori
    Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci) Läkemedelskemi Fysikalisk kemi Teoretisk kemi
    Forskningsämne
    Biokemi; Fysikalisk kemi
    Identifikatorer
    urn:nbn:se:oru:diva-4624 (URN)10.1016/j.cplett.2008.08.021 (DOI)000259150400035 ()2-s2.0-51349091343 (Scopus ID)
    Tillgänglig från: 2008-10-13 Skapad: 2008-10-13 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
    4. Computational Insights into the Mechanism of Substrate Binding in Potphobilinogen Synthase
    Öppna denna publikation i ny flik eller fönster >>Computational Insights into the Mechanism of Substrate Binding in Potphobilinogen Synthase
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Teoretisk kemi Fysikalisk kemi
    Forskningsämne
    Fysikalisk kemi
    Identifikatorer
    urn:nbn:se:oru:diva-9948 (URN)
    Tillgänglig från: 2010-03-12 Skapad: 2010-03-10 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
    5. Modelling the mechanism of porphobilinogen synthase
    Öppna denna publikation i ny flik eller fönster >>Modelling the mechanism of porphobilinogen synthase
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Fysikalisk kemi Teoretisk kemi
    Forskningsämne
    Fysikalisk kemi; Biokemi
    Identifikatorer
    urn:nbn:se:oru:diva-9949 (URN)
    Tillgänglig från: 2010-03-12 Skapad: 2010-03-10 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
    6. Computational insights into the first branching point in porphyrin biosynthesis: decarboxylation of ring D in URO–III by Uroporphyrinogen–III Decarboxylase
    Öppna denna publikation i ny flik eller fönster >>Computational insights into the first branching point in porphyrin biosynthesis: decarboxylation of ring D in URO–III by Uroporphyrinogen–III Decarboxylase
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Fysikalisk kemi Teoretisk kemi
    Forskningsämne
    Fysikalisk kemi; Biokemi
    Identifikatorer
    urn:nbn:se:oru:diva-9950 (URN)
    Tillgänglig från: 2010-03-12 Skapad: 2010-03-10 Senast uppdaterad: 2019-12-13Bibliografiskt granskad
  • 7.
    Erdtman, Edvin
    et al.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Bushnell, Eric A. C.
    Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada.
    Gauld, James W.
    Department of Chemistry and Biochemistry, University of Windsor, Windsor ON, Canada.
    Eriksson, Leif A.
    School of Chemistry, National University of Ireland (NUI Galway), Galway, Ireland.
    Computational studies on Schiff-base formation: Implications for the catalytic mechanism of porphobilinogen synthase2011Ingår i: Computational and Theoretical Chemistry, ISSN 2210-271X, E-ISSN 2210-2728, Vol. 963, nr 2-3, s. 479-489Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Schiff bases are common and important intermediates in many bioenzymatic systems. The mechanism by which they are formed, however,is dependent on the solvent, pH and other factors. In the present study we have used density functional theory methods in combination with appropriate chemical models to get a better understanding of the inherent chemistry of the formation of two Schiff bases that have been proposed to be involved in the catalytic mechanism of porphobilinogensynthase (PBGS), a key enzyme in the biosynthesis of porphyrins. More specifically, we have investigated the uncatalysed reaction of its substrate 5-aminolevulinic acid (5-ALA) with a lysine residue for theformation of the P-site Schiff base, and as possibly catalysed by the second active site lysine, water or the 5-ALA itself. It is found that cooperatively both the second lysine and the amino group of the initial 5-ALA itself are capable of reducing the rate-limiting energy barrier to14.0 kcal mol-1. We therefore propose these to be likely routes involved in the P-site Schiff-base formation in PBGS.

  • 8.
    Erdtman, Edvin
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    dos Santos, Daniel J. V. A.
    Löfgren, Lennart
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer2008Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 463, nr 1-3, s. 178-182Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    5-Aminolevulinic acid (5ALA) and ester derivates thereof are used as prodrugs in photodynamic therapy (PDT). The behavior of 5ALA and three esters of 5ALA in a DPPC lipid bilayer is investigated. In particular, the methyl ester displays a very different free energy profile, where the highest barrier is located in the region with highest lipid density, while the others have their peak in the middle of the membrane, and also displays a considerably lower permeability coefficient than neutral 5ALA and the ethyl ester. The zwitterion of 5ALA has the highest permeability constant, but a significant free energy minimum in the polar head-group region renders an accumulation in this region.

  • 9.
    Erdtman, Edvin
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical study of 5-aminolevulinic acid (5ALA) and some pharmaceutically important derivatives2007Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 434, nr 1-3, s. 101-106Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    5-Aminolevulinic acid (5ALA) is the key synthetic building block in protoporphyrin IX (PpIX), the heme chromophore in mitochondria. The addition of extracorporeal 5ALA and its alkyl ester derivatives are in current clinical use in photodynamical diagnostics and photodynamic therapy of tumors and skin disorders. In the current study density functional theory calculations are performed on 5ALA and its methyl, ethyl, and hexyl esters, in order to explore the basic chemical properties of these species. It is concluded that even in aqueous media the zwitterionic form of 5ALA is less stable than the non-zwitterionic one, that the local environment (lipid vs water) affects the energetics of reaction considerably, and that the hexyl species is most prone to hydrolysis of the three alkyl ester derivatives.

  • 10.
    Erdtman, Edvin
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical study of 5-aminolevulinic acid tautomerization: a novel self-catalyzed mechanism2008Ingår i: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 112, nr 18, s. 4367-4374Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    5-Aminolevulinic acid (5ALA) is the key synthetic building block in protoporphyrin IX (PpIX), the heme chromophore in mitochondria. In this study density functional theory calculations were performed on the tautomers of 5ALA and the tautomerization reaction mechanism from its enolic forms (5-amino-4-hydroxypent-3-enoic acid and 5-amino-4-hydroxypent-4-enoic acid) to the more stable 5ALA. The hydrated form 5-amino-4,4-dihydroxypentanoic acid was also studied. The lowest energy pathway of 5ALA tautomerization is by means of autocatalysis, in that an oxygen of the carboxylic group transfers the hydrogen atom as a "crane", with an activation energy of similar to 15 kcal/mol. This should be compared to the barriers of about 35 kcal/mol for water assisted tautomerization, and 60 kcal/mol for direct hydrogen transfer. For hydration of 5ALA, the water catalyzed activation barrier is found to be similar to 35 kcal/mol, approximately 5 kcal/mol lower than direct hydration.

  • 11.
    Erdtman, Edvin
    et al.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Gauld, James W
    Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B.
    Eriksson, Leif A.
    School of Chemistry, NUI Galway, Galway, Ireland.
    Computational Insights into the Mechanism of Substrate Binding in Potphobilinogen SynthaseManuskript (preprint) (Övrigt vetenskapligt)
  • 12.
    Erdtman, Edvin
    et al.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Gauld, James W.
    Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario N9B.
    Eriksson, Leif A.
    School of Chemistry, NUI Galway, Galway, Ireland.
    Modelling the mechanism of porphobilinogen synthaseManuskript (preprint) (Övrigt vetenskapligt)
  • 13.
    Eriksson, Leif A.
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Russo, Nino
    Ugalde, Jesus M.
    Second International Theoretical Biophysics Symposium, Örebro University, Sweden, June 28–July 1, 20052007Ingår i: International Journal of Quantum Chemistry, ISSN 0020-7608, E-ISSN 1097-461X, Vol. 107, nr 2, s. 66s. 259-260Artikel i tidskrift (Refereegranskat)
  • 14.
    Eriksson, Leif A.
    et al.
    Göteborgs universitet, Göteborg.
    Sirsjö, Allan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Tetrazole derivatives as cytochrome p450 inhibitors2019Patent (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    According to the invention there is provided a compound of formula I, wherein Rand Rhave meanings given in the description, which compounds are useful in the treatment of skin disorders and other diseases.

  • 15. Grand, André
    et al.
    Morell, C
    Labet, Vanessa
    Cadet, Jean
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    *H and *OH radical reactions with 5-methylcytosine2007Ingår i: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 111, nr 37, s. 8968-8972Artikel i tidskrift (Refereegranskat)
  • 16. Guedes, Rita Cardoso
    et al.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Photophysics, photochemistry, and reactivity: Molecular aspects of perylenequinone reactions2007Ingår i: Photochemical and Photobiological Sciences, ISSN 1474-905X, E-ISSN 1474-9092, Vol. 6, nr 10, s. 1089-1096Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were used to elucidate the photochemistry and photophysics of eight different perylenequinones (PQ). The objective of this work has been to quantitatively investigate the photodynamic therapeutic potential of this family of compounds and give an overview of their photoreactivity. The effects of solvation were evaluated through single-point calculations using the integral equation formalism of the polarised continuum model. It is concluded that the eight studied perylenequinones can generate singlet oxygen (in aqueous solution) and superoxide radical anions, and that the autoionisation of two nearby PQ molecules is possible.

  • 17. Jarikote, Dilip V.
    et al.
    Li, Wei
    Jiang, Tao
    Eriksson, Leif A.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Murphy, Paul V.
    Towards echinomycin mimetics by grafting quinoxaline residues on glycophane scaffolds2011Ingår i: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 19, nr 2, s. 826-835Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Echinomycin is a natural depsipeptide, which is a bisintercalator, inserting quinoxaline units preferentially adjacent to CG base pairs of DNA. Herein the design and synthesis of echinomycin mimetics based on grafting of two quinoxaline residues onto a macrocyclic scaffold (glycophane) is addressed. Binding of the compounds to calf-thymus DNA was studied using UV-vis and steady state fluorescence spectroscopy, as well as thermal denaturation. An interesting observation was enhancement of fluorescence emission for the peptidomimetics on binding to DNA, which contrasted with observations for echinomycin. Molecular dynamics simulations were exploited to explore in more detail if bis-intercalation to DNA was possible for one of the glycophanes. Bis-intercalating echinomycin complexes with DNA were found to be stable during 20 ns simulations at 298 K. However, the MD simulations of a glycophane complexed with a DNA octamer displayed very different behaviour to echinomycin and its quinoxaline units were found to rapidly migrate out from the intercalation site. Release of bis-intercalation strain occurred with only one of the quinoxaline chromophores remaining intercalated throughout the simulation. The distance between the quinoxaline residues in the glycophane at the end of the MD simulation was 7.3-7.5 angstrom, whereas in echinomycin, the distance between the residues was similar to 11 angstrom, suggesting that longer glycophane scaffolds would be required to generate bis-intercalating echinomycin mimetics. (C) 2010 Elsevier Ltd. All rights reserved.

  • 18.
    Karlsson, Magnus
    et al.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Strid, Åke
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Sirsjö, Allan
    Örebro universitet, Hälsoakademin.
    Eriksson, Leif A.
    Örebro universitet, Akademin för naturvetenskap och teknik.
    Homology Models and Molecular Modeling of Human Retinoic Acid Metabolizing Enzymes Cytochrome P450 26A1 (CYP26A1) and P450 26B1 (CYP26B1)2008Ingår i: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 4, nr 6, s. 1021-1027Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Homology models of cytochrome P450 26A1 and cytochrome P450 26B1 were constructed using the crystal structures of human, CYP2C8, CYP2C9, and CYP3A4 as templates for the model building. The homology models generated were investigated for their docking capacities against the natural substrate all-trans-retinoic acid (atRA), five different tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs), and R115866. Interaction energies (IE) and linear interaction energies (LIE) were calculated for all inhibitors in both homology models after molecular dynamics (MD) simulation of the enzyme-ligand complexes. The results revealed that the homologues had the capacity to distinguish between strong and weak inhibitors. Important residues in the active site were identified from the CYP26A1/B1-atRA complexes. Residues involved in hydrophobic interactions with atRA were Pro113, Phe222, Phe299, Val370,

    Pro371, and Phe374 in CYP26A1 and Leu88, Pro118, Phe222, Phe295, Ile368, and Tyr272 in CYP26B1. Hydrogen bonding interactions were observed between the atRA carboxylate group and Arg 90 in CYP26A1 and with Arg76, Arg95, and Ser369 in CYP26B1.

  • 19. Labet, Vanessa
    et al.
    Grand, André
    Morell, Christophe
    Cadet, Jean
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Proton catalyzed hydrolytic deamination of cytosine: a computational study2008Ingår i: Theoretical Chemistry accounts, ISSN 1432-881X, E-ISSN 1432-2234, Vol. 120, nr 4-6, s. 429-435Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Two pathways involving proton catalyzed hydrolytic deamination of cytosine (to uracil) are investigated at the PCM-corrected B3LYP/6-311G(d,p) level of theory, in the presence of an additional catalyzing water molecule. It is concluded that the pathway involving initial protonation at nitrogen in position 3 of the ring, followed by water addition at C4 and proton transfer to the amino group, is a likely route to hydrolytic deamination. The rate determining step is the addition of water to the cytosine, with a calculated free energy barrier in aqueous solution of G==140 kJ/mol. The current mechanism provides a lower barrier to deamination than previous work based on OH− catalyzed reactions, and lies closer to the experimental barrier derived from rate constants (Ea = 117 ± 4kJ/mol).

  • 20.
    Matxain, Jon M
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A
    Örebro universitet, Institutionen för naturvetenskap.
    Mercero, Jose M
    Lopez, Xabier
    Piris, Mario
    Ugalde, Jesus M
    Poater, Jordi
    Matito, E
    Solá, Miguel
    New solids based on B12N12 fullerenes2007Ingår i: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 111, nr 36, s. 13354-60Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In recent years, BN fullerenes have been synthesized experimentally. As their carbon counterparts, these BN fullerenes could be assembled in molecular solids, but this possibility has been studied little in the literature. In this work, we focus on the smallest synthesized BN fullerene, B12N12, which is built by squares and hexagons. First, the interaction between two of these fullerenes has been analyzed, using the hybrid B3LYP and MPW1PW91 density functional methods. Two different interactions have been studied in the dimer, a square facing a square (S−S) and a hexagon facing a hexagon (H−H). In both cases, a B is facing a N. The most stable dimer was found to be S−S facing, with covalent interactions between the monomers, but other dimers with weak interactions have been found as well, which opens possibilities of new systems, as in the case of fullerene dimers and solids. The solids resulting from the infinite repetition of the characterized dimers were optimized, finding two different solids, with covalent and weak interactions between monomers, respectively. The solid with covalent interactions is a nanoporous material that is more stable by around 12 eV. Because of the nanoporous character of this solid, it could be used for heterogeneous catalysis, molecular transport, and so forth. The SIESTA code with the GGA-PBE density functional method has been used for the solid-state calculations.

  • 21.
    Musa, Klefah A. K.
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical assessment of naphazoline redoxchemistry and photochemistry2007Ingår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 15, s. 3977-3981Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The imidazoline derivative naphazoline (2-(1-naphtylmethyl)-2-imidazoline) is an α2-adrenergic agonist used as non-prescription eye and nasal preparations. Besides its functionality in generating vascoconstriction and decongestion in the patient, the toxicity, ROS generating capability, and recently also possible antioxidant capacity of the compound have been reported in the literature. In the current work the structural and electronic features of the drug are explored, using computational chemical tools. Electron affinities, ionization potentials, and excitation energies are reported, as well as charge and spin distributions of various forms of the drug. The difference in photochemical behavior between the protonated and unprotonated (basic) species is explained by the molecular orbital distributions, allowing for efficient excitation quenching in the basic structure but clear naphthalene to imidazolene charge transfer upon HOMO→ LUMO excitation in the protonated form, enabling larger intersystem crossing capability to the imidazole localized excited triplet and a resulting higher singlet oxygen quantum yield.

  • 22.
    Musa, Klefah A. K.
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical Study of Ibuprofen Phototoxicity2007Ingår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 46, s. 13345-13352Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The photochemical properties and degradation of the common nonsteroid anti-inflammatory drug ibuprofen is studied by means of hybrid density functional theory. Computed energies and properties of various species show that the deprotonated form dominates at physiological pH, and that the species will not be able to decarboxylate from a singlet excited state. Instead, decarboxylation will occur, with very high efficiency, provided the deprotonated compound can undergo intersystem crossing from an excited singlet to its excited triplet state. In the triplet state, the C−C bond connecting the carboxyl group is elongated, and the CO2 moiety detaches with a free energy barrier of less than 0.5 kcal/mol. Depending on the local environment, the decarboxylated product can then either be quenched through intersystem crossing (involving the possible formation of singlet oxygen) and protonation, or serve as an efficient source for superoxide anions and the formation of a peroxyl radical that will initiate lipid peroxidation.

  • 23.
    Musa, Klefah A K
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Matxain, Jon M
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A
    Örebro universitet, Institutionen för naturvetenskap.
    Mechanism of Photoinduced Decomposition of Ketoprofen2007Ingår i: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 50, nr 8, s. 1735-1743Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UV-induced decarboxylation of the NSAID ketoprofen, followed by activation of molecular oxygen or formation of a decarboxylated peroxide adduct, is explored using computational quantum chemistry. The excited energy surfaces reveal that the neutral species will not decarboxylate, whereas the deprotonated acid decarboxylates spontaneously in the triplet state, and with an associated 3-5 kcal/mol barrier from several low-lying excited singlet states. The observed long lifetimes of the decarboxylated anion is explained in terms of the high stability of the triplet benzoyl ethyl species with protonated carbonylic oxygen, from which there is no obvious decay channel. Mechanisms for the generation of singlet oxygen and superoxide are discussed in detail. Addition of molecular oxygen to give the corresponding peroxyl radical capable of initiating propagating lipid peroxidation reactions is also explored. The computed data explains all features of the observed experimental observations made to date on the photodegradation of ketoprofen.

  • 24.
    Musa, Klefah A.K.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical studies of photodynamic drugs and phototoxic reactions2007Licentiatavhandling, monografi (Övrigt vetenskapligt)
  • 25.
    Saenz-Mendez, Patricia
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Guedes, Rita C.
    dos Santos, Daniel J.V.A.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical prediction of binding modes and hot sequences for allopsoralen-DNA interaction2007Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 450, nr 1-3, s. 127-131Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Molecular docking studies of two duplex DNA sequences as target fragments and allopsoralen as ligand were performed. The calculated interaction energies showed that the ligand can be docked into the minor groove as well as become intercalated. However, unlike psoralen, allopsoralen preferred binding mode for non-poly-TA sequences is minor groove binding. Calculated energies for intercalation between different base pairs suggest that the predicted sequence selectivity for allopsoralen is analogous to that observed for psoralen. Intercalation is favored in 5'-TpA sites in poly-TA sequences.

  • 26.
    Saenz-Mendez, Patricia
    et al.
    Örebro universitet, Institutionen för naturvetenskap.
    Guedes, Rita C.
    dos Santos, Daniel J.V.A.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical study of sequence selectivity and preferred binding mode of psoralen with DNA2007Ingår i: Research Letters in Physical Chemistry, ISSN 1687-6873, s. Article number 60623-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Psoralen interaction with two models of DNA was investigated using molecular mechanics and molecular dynamics methods. Calculated energies of minor groove binding and intercalation were compared in order to define a preferred binding mode for the ligand.We found that both binding modes are possible, explaining the low efficiency for monoadduct formation from intercalated ligands. A comparison between the interaction energy for intercalation between different base pairs suggests that the observed sequence selectivity is due to favorable intercalation in 5'-TpA in (AT)n sequences.

  • 27.
    Saenz-Méndez, Patricia
    et al.
    Computational Chemistry and Biology Group, Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay.
    Elmabsout, Ali Ateia
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Sävenstrand, Helena
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Awadalla, Mohamed Khalid Alhaj
    Department of Clinical Medicine, School of Health Sciences, Örebro University, Örebro, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Sirsjö, Allan
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Eriksson, Leif A.
    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
    Homology models of human all-trans-retinoic acid metabolizing enzymes CYP26B1 and CYP26B1 spliced-variant2012Ingår i: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 52, nr 10, s. 2631-2637Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Homology models of CYP26B1 (cytochrome P450RAI2) and CYP26B1 spliced-variant were derived using the crystal structure of cyanobacterial CYP120A1 as template for the model building. The quality of the homology models generated were carefully evaluated, and the natural substrate all-trans-retinoic acid (atRA), several tetralone-derived retinoic acid metabolizing blocking agents (RAMBAs) and a well known potent inhibitor of CYP26B1 (R115866) were docked into the homology model of full-length cytochrome P450 26B1. The results show that in the model of the full length CYP26B1, the protein is capable of distinguishing between the natural substrate (atRA), R115866 and the tetralone derivatives. The spliced-variant of CYP26B1 model displays a reduced affinity for atRA compared to the full length enzyme, in accordance with recently described experimental information.

  • 28. Sebastian, Eider San
    et al.
    Matxain, Jon M.
    Örebro universitet, Institutionen för naturvetenskap.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Stote, Roland H.
    Dejaegere, Annick
    Cossio, Fernando P.
    Lopez, Xabier
    Metal ion dependent adhesion sites in integrins: A Combined DFT and QMC Study on Mn2+2007Ingår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 30, s. 9099-9103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The theoretical study of relative energies of different spin states of Mn2+ has been carried out for the isolated cation and for structures in which the cation is coordinated to ligands that represent the first coordination shell in a protein environment that contains a metal ion dependent adhesion site (MIDAS, found in the ligand binding domain of protein LFA-1). The calculations determine whether the ligand field generated by a prototype protein environment affects the relative energies between high, intermediate, and low spin states. Geometry optimizations and vibrational frequency calculations were carried out at the B3LYP/SKBJ+* level of theory. Single point calculations were performed at the B3LYP/6-311++G(2df,2p) and diffusion monte carlo (DMC) levels for the refinement of the electronic energies. These calculations reveal important differences in the relative energies between high/low spin complexes obtained by B3LYP and DMC and show that although both DFT and DMC show similar trends, a higher level method such as DMC is necessary for a quantitative description of the interactions between Mn2+ and its natural ligands. (G)s of acetate-type ligand binding reactions were calculated that show that the higher the spin of the manganese complex, the lower the affinity for the ligand.

  • 29. Tejero, Ismael
    et al.
    Gonzalez-Lafont, Angels
    Lluch, José M.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Theoretical modeling of hydroxyl-radical-induced lipid peroxidation reactions2007Ingår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 20, s. 5684-5693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The OH-radical-induced mechanism of lipid peroxidation, involving hydrogen abstraction followed by O2 addition, is explored using the kinetically corrected hybrid density functional MPWB1K in conjunction with the MG3S basis set and a polarized continuum model to mimic the membrane interior. Using a small nonadiene model of linoleic acid, it is found that hydrogen abstraction preferentially occurs at the mono-allylic methylene groups at the ends of the conjugated segment rather than at the central bis-allylic carbon, in disagreement with experimental data. Using a full linoleic acid, however, abstraction is correctly predicted to occur at the central carbon, giving a pentadienyl radical. The Gibbs free energy for abstraction at the central C11 is 8 kcal/mol, compared to 9 kcal/mol at the end points (giving an allyl radical). Subsequent oxygen addition will occur at one of the terminal atoms of the pentadienyl radical fragment, giving a localized peroxy radical and a conjugated butadiene fragment, but is associated with rather high free energy barriers and low exergonicity at the CPCM-MPWB1K/MG3S level. The ZPE-corrected potential energy surfaces obtained without solvent effects, on the other hand, display considerably lower barriers and more exergonic reactions.

  • 30.
    Tian, Li-Yun
    et al.
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
    Levämäki, Henrik
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden.
    Eriksson, Olle
    Örebro universitet, Institutionen för naturvetenskap och teknik. Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden.
    Kokko, Kalevi
    Department of Physics and Astronomy, University of Turku, Turku, Finland; Turku University Centre for Materials and Surfaces (MatSurf), Turku, Finland.
    Nagy, Ágnes
    Department of Theoretical Physics, University of Debrecen, Debrecen, Hungary.
    Délczeg-Czirják, Erna Krisztina
    Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden.
    Vitos, Levente
    Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology, Stockholm, Sweden; Department of Physics and Astronomy, Division of Materials Theory, Uppsala University, Uppsala, Sweden; Research Institute for Solid State Physics and Optics, Wigner Research Center for Physics, Budapest, Hungary.
    Density Functional Theory description of the order-disorder transformation in Fe-Ni2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, nr 1, artikel-id 8172Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The thermodynamic ordering transformation of tetragonal FeNi system is investigated by the Exact Muffin-Tin Orbitals (EMTO) method. The tetragonal distortion of the unit cell is taken into account and the free energy is calculated as a function of long-range order and includes the configurational, vibrational, electronic and magnetic contributions. We find that both configurational and vibrational effects are important and that the vibrational effect lowers the predicted transformation temperature by about 480 K compared to the value obtained merely from the configurational free energy. The predicted temperature is in excellent agreement with the experimental value when all contributions are taken into account. We also perform spin dynamics calculations for the magnetic transition temperature and find it to be in agreement with the experiments. The present research opens new opportunities for quantum-mechanical engineering of the chemical and magnetic ordering in tetrataenite.

  • 31.
    Wu, Min
    et al.
    Chalmers University of Technology, Gothenburg, Sweden.
    Farkas, Daniel
    Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden; School of Science and Technology, Örebro University, Örebro, Sweden.
    Eriksson, Leif A.
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Proline 411 biases the conformation of the intrinsically disordered plant UVR8 photoreceptor C27 domain altering the functional properties of the peptide2019Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, artikel-id 818Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UVR8 (UV RESISTANCE LOCUS 8) is a UV-B photoreceptor responsible for initiating UV-B signalling in plants. UVR8 is a homodimer in its signalling inactive form. Upon absorption of UV radiation, the protein monomerizes into its photoactivated state. In the monomeric form, UVR8 binds the E3 ubiquitin ligase COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1), triggering subsequent UV-B-dependent photomorphogenic development in plants. Recent in vivoexperiments have shown that the UVR8 C-terminal region (aa 397-423; UVR8C27) alone is sufficient to regulate the activity of COP1. In this work, CD spectroscopy and NMR experiments showed that the UVR8C27domain was non-structured but gained secondary structure at higher temperatures leading to increased order. Bias-exchange metadynamics simulations were also performed to evaluate the free energy landscape of UVR8C27. An inverted free energy landscape was revealed, with a disordered structure in the global energy minimum. Flanking the global energy minimum, more structured states were found at higher energies. Furthermore, stabilization of the low energy disordered state was attributed to a proline residue, P411, as evident from P411A mutant data. P411 is also a key residue in UVR8 binding to COP1. UVR8C27is therefore structurally competent to function as a molecular switch for interaction of UVR8 with different binding partners since at higher free energies different structural conformations are being induced in this peptide. P411 has a key role for this function.

  • 32.
    Wu, Min
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Eriksson, Leif
    University of Gothenburg, Gothenburg, Sweden.
    Prediction of the thre-dimensional structure of the plant UVR8 photoreceptor dimer, and the key residues in UV-B regulated signalling pathway2012Ingår i: Science and Technology Day 2012.: Poster exhibition, 2012, s. C28-C28Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    See attachment

  • 33.
    Wu, Min
    et al.
    Gothenburg University, Gothenburg, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Eriksson, Leif
    Gothenburg University, Gothenburg, Sweden.
    Umbrella sampling calculations of the bindning free energy in the UVR8 dimer.: key residues in uv-b regulated signalling pathway revealed using dft and md simulation methods2012Ingår i: Challenges in biomolecular modeling: from qm to coarse-graining. International Society of Quantum Biology and Pharmacology / [ed] Lennart Nilsson, Stockholm, 2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    The dimeric UVR8 protein is a ultraviolet-B radiation (280-315 nm) photoreceptor that is responsible for the first step in UV-B regulation of gene expression in plants1. Its action comprises the actual absorption of the UV quanta by a Trp array in the protein, followed by monomerisation, and subsequent aggregation with downstream signaling components2. Quantum theoretical DFT calculationsa of excitation spectra of both a large cluster model involving seven tryptophans at the interface of the UVR8 proteins where they are intermixed with positive residues (mainly arginines) and a couple of tyrosines, and smaller fragments thereof, reveal that absorption maxima appearing in the 280-300 nm range for the full cluster result from interactions between the central tryptophans and surrounding arginines2. This observation provides an explanation for the experimentally measured action spectrum of the UVR8-dependent UV-B stimulation of HY5 transcription in mature A. thaliana leaf tissue3. Umbrella sampling methodb was used to calculate the binding free energy for the wild type UVR8 dimer and three of its mutants (R286A, R338A and R286A/R338A), in order to verify the key mutants able to disrupt the dimeric structure.

    See also attached document.

  • 34.
    Wu, Min
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Eriksson, Leif A.
    University of Gothenburg, Gothenburg, Sweden.
    Development of non-standard arginine residue parameters for use with the AMBER force fields2013Ingår i: Chemical Physics Letters, ISSN 0009-2614, E-ISSN 1873-4448, Vol. 584, s. 188-194Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Amino acid radicals are often involved as intermediates in biological processes, but are difficult to capture by experiment. Computational modeling can be employed to study the features of the species involved. The neutral arginyl radical has previously been detected experimentally using ECD and ETD spectroscopy. Protonation of the radical can occur on the guanidinium carbon, depending on the peptide structure and protein environment. Accurate force fields are essential for reproducing the conformational and dynamic behavior of these intermediates. New AMBER ff99 parameters for the arginyl radical and hydrogenated arginyl side chains are presented based on ab initio quantum chemical calculations. (c) 2013 Elsevier B.V. All rights reserved.

  • 35.
    Wu, Min
    et al.
    University of Gothenburg, Gothenburg, Sweden.
    Strid, Åke
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Eriksson, Leif A
    University of Gothenburg, Gothenburg, Sweden.
    Interactions and Stabilities of the UV RESISTANCE LOCUS8 (UVR8) protein dimer and its key mutants2013Ingår i: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 53, nr 7, s. 1736-1746Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dimeric UVR8 protein is a ultraviolet-B radiation (280-315 nm) photoreceptor responsible for the first step in UV-B regulation of gene expression in plants. Its action comprises the actual absorption of the UV quanta by a tryptophan array at the protein-protein interface, followed by monomerisation, and subsequent aggregation with downstream signaling components. A crystal structure of the Arabidopsis thaliana tryptophan-rich wild type UVR8 protein dimer was recently published, showing the presence of several salt bridges involving arginines R146, R286, R338 and R354. In this work, molecular dynamics simulations in conjunction with umbrella sampling was used to calculate the binding free energy for the wild type UVR8 dimer and three of its mutants (R286A, R338A and R286A/R338A), in order to verify whether the key mutants are able to disrupt the dimeric structure as indicated experimentally.

  • 36. Zhang, Ru bo
    et al.
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Effects of OH radical addition on proton transfer in the guanine-cytosine base pair2007Ingår i: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 111, nr 23, s. 6571-6576Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Double proton transfer (PT) reactions in guanine-cytosine OH radical adducts are studied by the hybrid density functional B3LYP approach. Concerted and stepwise proton-transfer processes are explored between N1(H) on guanine (G) and N3 on cytosine (C), and between N4(H) on C and O6 on G. All systems except GC6OH display a concerted mechanism. 8OHGC has the highest dissociation energy and is 1.2 kcal/mol more stable than the nonradical GC base pair. The origin of the interactions are investigated through the estimation of intrinsic acid-basic properties of the *OH-X monomer (X = G or C). Solvent effects play a significant role in reducing the dissociation energy. The reactions including *OH-C adducts have significantly lower PT barriers than both the nonradical GC pair and the *OH-G adducts. All reactions are endothermic, with the GC6OH --> GC6OHPT reaction has the lowest reaction energy (4.6 kcal/mol). In accordance with earlier results, the estimated NBO charges show that the G moiety carries a slight negative charge (and C a corresponding positive one) in each adduct. The formation of a partial ion pair may be a potential factor leading to the PT reactions being thermodynamically unfavored.

  • 37. Zhang, Ru Bo
    et al.
    Gao, Feng xin
    Eriksson, Leif A.
    Örebro universitet, Institutionen för naturvetenskap.
    Radical-induced damage in 3'dTMP: Insights into a mechanism for DNA strand cleavage2007Ingår i: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 3, nr 3, s. 803-810Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    DNA strand scission and base release in 3‘dTMP, induced by H and OH radical addition to thymine, is studied at the DFT B3LYP/6-31+G(d,p) level in the gas phase and in solution. In particular the mechanism of H atom transfer subsequent to radical formation, from C2‘ on the sugar to the C6 site on the base, is explored. Bulk solvation is found to lower the barrier by up to 5 kcal mol-1 and the reaction energy by up to 12 kcal mol-1 for the hydroxyl radical adducts. The strengths of the N1−C1‘(N1-glycosidic bond) and C3‘−O(P) bonds are calculated, showing that homolytic bond breaking processes are largely favored in both cases. The barrier for C3‘−O(P) bond rupture is approximately 18.2 kcal mol-1, and its breakage is preferred by 10−15 kcal mol-1 over that of N1-glycosidic bond cleavage in both the gas phase and solvents, which is consistent with the changes in C3‘−O(P) and N1−C1‘ bond lengths during the H transfer reactions. Mulliken spin densities, NPA charges, and vertical electron affinities are calculated to clarify the reactive properties of the intramolecular H-transfer radicals.

1 - 37 av 37
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf