1of1
From Proteopedia
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'''KINETICS AND CRYSTAL STRUCTURE OF THE HERPES SIMPLEX VIRUS TYPE 1 THYMIDINE KINASE INTERACTING WITH (SOUTH)-METHANOCARBA-THYMIDINE''' | '''KINETICS AND CRYSTAL STRUCTURE OF THE HERPES SIMPLEX VIRUS TYPE 1 THYMIDINE KINASE INTERACTING WITH (SOUTH)-METHANOCARBA-THYMIDINE''' | ||
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[[Category: Schelling, P.]] | [[Category: Schelling, P.]] | ||
[[Category: Schulz, G E.]] | [[Category: Schulz, G E.]] | ||
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| - | [[Category: | + | [[Category: Kinase]] |
| - | [[Category: | + | [[Category: Thymidine kinase]] |
| - | [[Category: | + | [[Category: Transferase]] |
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Revision as of 00:45, 3 May 2008
KINETICS AND CRYSTAL STRUCTURE OF THE HERPES SIMPLEX VIRUS TYPE 1 THYMIDINE KINASE INTERACTING WITH (SOUTH)-METHANOCARBA-THYMIDINE
Overview
Chondroitinase B from Pedobacter heparinus is the only known enzyme strictly specific for dermatan sulfate and is a widely used enzymatic tool for the structural characterization of glycosaminoglycans. This beta-helical polysaccharide lyase belongs to family PL-6 and cleaves the beta(1,4) linkage of dermatan sulfate in a random manner, yielding 4,5-unsaturated dermatan sulfate disaccharides as the product. The previously reported structure of its complex with a dermatan sulfate disaccharide product identified the -1 and -2 subsites of the catalytic groove. We present here the structure of chondroitinase B complexed with several dermatan sulfate and chondroitin sulfate oligosaccharides. In particular, the soaking of chondroitinase B crystals with a dermatan sulfate hexasaccharide results in a complex with two dermatan sulfate disaccharide reaction products, enabling the identification of the +2 and +1 subsites. Unexpectedly, this structure revealed the presence of a calcium ion coordinated by sequence-conserved acidic residues and by the carboxyl group of the l-iduronic acid at the +1 subsite. Kinetic and site-directed mutagenesis experiments have subsequently demonstrated that chondroitinase B absolutely requires calcium for its activity, indicating that the protein-Ca(2+)-oligosaccharide complex is functionally relevant. Modeling of an intact tetrasaccharide in the active site of chondroitinase B provided a better understanding of substrate specificity and the role of Ca(2+) in enzymatic activity. Given these results, we propose that the Ca(2+) ion neutralizes the carboxyl moiety of the l-iduronic acid at the cleavage site, whereas the conserved residues Lys-250 and Arg-271 act as Bronsted base and acid, respectively, in the lytic degradation of dermatan sulfate by chondroitinase B.
About this Structure
1OF1 is a Single protein structure of sequence from Human herpesvirus 1. Full crystallographic information is available from OCA.
Reference
The structure of chondroitin B lyase complexed with glycosaminoglycan oligosaccharides unravels a calcium-dependent catalytic machinery., Michel G, Pojasek K, Li Y, Sulea T, Linhardt RJ, Raman R, Prabhakar V, Sasisekharan R, Cygler M, J Biol Chem. 2004 Jul 30;279(31):32882-96. Epub 2004 May 21. PMID:15155751 Page seeded by OCA on Sat May 3 03:45:53 2008
