2fuq

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spinqualitylabelsall models 2fuq, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Heparinase II

Overview

Heparinase II depolymerizes heparin and heparan sulfate, glycosaminoglycans, yielding unsaturated oligosaccharide products through, an elimination degradation mechanism. This enzyme cleaves the, oligosaccharide chain on the nonreducing end of either glucuronic or, iduronic acid, sharing this characteristic with a chondroitin ABC lyase., We have determined the first structure of a heparin-degrading lyase, that, of heparinase II from Pedobacter heparinus (formerly Flavobacterium, heparinum), in a ligand-free state at 2.15 A resolution and in complex, with a disaccharide product of heparin degradation at 2.30 A resolution., The protein is composed of three domains: an N-terminal alpha-helical, domain, a central two-layered beta-sheet domain, and a C-terminal domain, forming a two-layered beta-sheet. Heparinase II shows overall structural, similarities to the polysaccharide lyase family 8 (PL8) enzymes, chondroitin AC lyase and hyaluronate lyase. In contrast to PL8 enzymes, however, heparinase II forms stable dimers, with the two active sites, formed independently within each monomer. The structure of the N-terminal, domain of heparinase II is also similar to that of alginate lyases from, the PL5 family. A Zn2+ ion is bound within the central domain and plays an, essential structural role in the stabilization of a loop forming one wall, of the substrate-binding site. The disaccharide binds in a long, deep, canyon formed at the top of the N-terminal domain and by loops extending, from the central domain. Based on structural comparison with the lyases, from the PL5 and PL8 families having bound substrates or products, the, disaccharide found in heparinase II occupies the "+1" and "+2" subsites., The structure of the enzyme-product complex, combined with data from, previously characterized mutations, allows us to propose a putative, chemical mechanism of heparin and heparan-sulfate degradation.

About this Structure

2FUQ is a Single protein structure of sequence from Pedobacter heparinus with , and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of heparinase II from Pedobacter heparinus and its complex with a disaccharide product., Shaya D, Tocilj A, Li Y, Myette J, Venkataraman G, Sasisekharan R, Cygler M, J Biol Chem. 2006 Jun 2;281(22):15525-35. Epub 2006 Mar 24. PMID:16565082

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