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1kug
From Proteopedia
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'''Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW''' | '''Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW''' | ||
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[[Category: Ko, T P.]] | [[Category: Ko, T P.]] | ||
[[Category: Wang, A H.J.]] | [[Category: Wang, A H.J.]] | ||
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| - | [[Category: | + | [[Category: Retro-binding manner]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:10:56 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 20:10, 2 May 2008
Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW
Overview
Venoms from crotalid and viperid snakes contain several peptide inhibitors which regulate the proteolytic activities of their snake-venom metalloproteinases (SVMPs) in a reversible manner under physiological conditions. In this report, we describe the high-resolution crystal structures of a SVMP, TM-3, from Taiwan habu (Trimeresurus mucrosquamatus) cocrystallized with the endogenous inhibitors pyroGlu-Asn-Trp (pENW), pyroGlu-Gln-Trp (pEQW) or pyroGlu-Lys-Trp (pEKW). The binding of inhibitors causes some of the residues around the inhibitor-binding environment of TM-3 to slightly move away from the active-site center, and displaces two metal-coordinated water molecules by the C-terminal carboxylic group of the inhibitors. This binding adopts a retro-manner principally stabilized by four possible hydrogen bonds. The Trp indole ring of the inhibitors is stacked against the imidazole of His143 in the S-1 site of the proteinase. Results from the study of synthetic inhibitor analogues showed the primary specificity of Trp residue of the inhibitors at the P-1 site, corroborating the stacking effect observed in our structures. Furthermore, we have made a detailed comparison of our structures with the binding modes of other inhibitors including batimastat, a hydroxamate inhibitor, and a barbiturate derivative. It suggests a close correlation between the inhibitory activity of an inhibitor and its ability to fill the S-1 pocket of the proteinase. Our work may provide insights into the rational design of small molecules that bind to this class of zinc-metalloproteinases.
About this Structure
1KUG is a Single protein structure of sequence from Protobothrops mucrosquamatus. Full crystallographic information is available from OCA.
Reference
Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues., Huang KF, Chiou SH, Ko TP, Wang AH, Eur J Biochem. 2002 Jun;269(12):3047-56. PMID:12071970 Page seeded by OCA on Fri May 2 23:10:56 2008
