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dc.contributor.authorCórdula, Carolina Ribeiro [UNIFESP]
dc.contributor.authorLima, Marcelo A. [UNIFESP]
dc.contributor.authorShinjo, Samuel K. [UNIFESP]
dc.contributor.authorGesteira, Tarsis F. [UNIFESP]
dc.contributor.authorPol-Fachin, Laercio
dc.contributor.authorCoulson-Thomas, Vivien Jane [UNIFESP]
dc.contributor.authorVerli, Hugo
dc.contributor.authorYates, Edwin A. [UNIFESP]
dc.contributor.authorRudd, Timothy R.
dc.contributor.authorPinhal, Maria A. S. [UNIFESP]
dc.contributor.authorToma, Leny [UNIFESP]
dc.contributor.authorDietrich, Carl P. [UNIFESP]
dc.contributor.authorNader, Helena B. [UNIFESP]
dc.contributor.authorTersariol, Ivarne L. S. [UNIFESP]
dc.identifier.citationMolecular Biosystems. Cambridge: Royal Soc Chemistry, v. 10, n. 1, p. 54-64, 2014.
dc.description.abstractThe structurally diverse polysaccharide lyase enzymes are distributed from plants to animals but share common catalytic mechanisms. One, heparinase I (F. heparinum), is employed in the production of the major anticoagulant drug, low molecular weight heparin, and is a mainstay of cell surface proteoglycan analysis. We demonstrate that heparinase I specificity and efficiency depend on the cationic form of the substrate. Ca2+-heparin, in which alpha-L-iduronate-2-O-sulfate residues adopt C-1(4) conformation preferentially, is a substrate, while Na+-heparin is an inhibitor. His and Tyr residues are identified in the catalytic step and a model based on molecular dynamics and docking is proposed, in which deprotonated His203 initiates beta-elimination by abstracting the C5 proton of the alpha-L-iduonate-2-O-sulfate residue in the substrate, and protonated Tyr357 provides the donor to the hexosamine leaving group.en
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipNational High Magnetic Field Laboratory
dc.publisherRoyal Soc Chemistry
dc.relation.ispartofMolecular Biosystems
dc.rightsAcesso restrito
dc.titleOn the catalytic mechanism of polysaccharide lyases: evidence of His and Tyr involvement in heparin lysis by heparinase I and the role of Ca2+en
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Liverpool
dc.contributor.institutionUniv Fed Rio Grande do Sul
dc.contributor.institutionDiamond Light Source Ltd
dc.contributor.institutionUniv Mogi das Cruzes
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv Liverpool, Dept Struct & Chem Biol, Liverpool L69 7ZB, Merseyside, England
dc.description.affiliationUniv Fed Rio Grande do Sul, Ctr Biotecnol, BR-91500970 Porto Alegre, RS, Brazil
dc.description.affiliationDiamond Light Source Ltd, Didcot OX11 ODE, Oxon, England
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, Ctr Ciencias Tecnol, BR-08780911 Mogi Das Cruzes, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, BR-04044020 São Paulo, Brazil
dc.description.sponsorshipIDCAPES: 172/2012
dc.description.sourceWeb of Science

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