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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:
Carolina R.
Córdula
(Universidade Federal de São Paulo)
,
Marcelo
Lima
(Universidade Federal de São Paulo)
,
Samuel K.
Shinjo
(Universidade Federal de São Paulo)
,
Tarsis F.
Gesteira
(Universidade Federal de São Paulo)
,
Laércio
Pol- Fachin
(Universidade Federal do Rio Grande do Sul)
,
Vivien J.
Coulson- Thomas
(Universidade Federal de São Paulo)
,
Hugo
Verli
(Universidade Federal do Rio Grande do Sul)
,
Edwin
Yates
(University of Liverpool; Universidade Federal de São Paulo)
,
Timothy
Rudd
(University of Liverpool, Diamond Light Source)
,
Maria A. S.
Pinhal
(Universidade Federal de São Paulo)
,
Leny
Toma
(Universidade Federal de São Paulo)
,
Carl P.
Dietrich
(Universidade Federal de São Paulo)
,
Helena B.
Nader
(Universidade Federal de São Paulo)
,
Ivarne L. S.
Tersariol
(Universidade Federal de São Paulo)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Molecular Biosystems
, VOL 10 (1)
, PAGES 54 - 64
State:
Published (Approved)
Published:
January 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 α-L-iduronate-2-O-sulfate residues adopt 1C4 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 β-elimination by abstracting the C5 proton of the α-L-iduonate-2-O-sulfate residue in the substrate, and protonated Tyr357 provides the donor to the hexosamine leaving group.
Diamond Keywords: Enzymes
Subject Areas:
Biology and Bio-materials,
Chemistry
Technical Areas:
Added On:
02/03/2016 10:29
Discipline Tags:
Biochemistry
Chemistry
Life Sciences & Biotech
Technical Tags: