Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/37256
Title: On the catalytic mechanism of polysaccharide lyases: evidence of His and Tyr involvement in heparin lysis by heparinase I and the role of Ca2+
Authors: Córdula, Carolina Ribeiro [UNIFESP]
Lima, Marcelo A. [UNIFESP]
Shinjo, Samuel K. [UNIFESP]
Gesteira, Tarsis F. [UNIFESP]
Pol-Fachin, Laercio
Coulson-Thomas, Vivien Jane [UNIFESP]
Verli, Hugo
Yates, Edwin A. [UNIFESP]
Rudd, Timothy R.
Pinhal, Maria A. S. [UNIFESP]
Toma, Leny [UNIFESP]
Dietrich, Carl P. [UNIFESP]
Nader, Helena B. [UNIFESP]
Tersariol, Ivarne L. S. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Univ Liverpool
Univ Fed Rio Grande do Sul
Diamond Light Source Ltd
Univ Mogi das Cruzes
Issue Date: 1-Jan-2014
Publisher: Royal Soc Chemistry
Citation: Molecular Biosystems. Cambridge: Royal Soc Chemistry, v. 10, n. 1, p. 54-64, 2014.
Abstract: The 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.
URI: http://repositorio.unifesp.br/handle/11600/37256
ISSN: 1742-206X
Other Identifiers: http://dx.doi.org/10.1039/c3mb70370c
Appears in Collections:Em verificação - Geral

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