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| {{STRUCTURE_1kuk| PDB=1kuk | SCENE= }} | | {{STRUCTURE_1kuk| PDB=1kuk | SCENE= }} |
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| '''Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with pEKW.'''
| | ===Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with pEKW.=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12071970}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12071970 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12071970}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Alpha/beta protein]] | | [[Category: Alpha/beta protein]] |
| [[Category: Retro-binding manner]] | | [[Category: Retro-binding manner]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:11:13 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:01:48 2008'' |