1kuk: Difference between revisions

[[Image:1kuk.jpg|left|200px]]<br /><applet load="1kuk" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1KUK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Protobothrops_mucrosquamatus Protobothrops mucrosquamatus] with <scene name='pdbligand=CD:'>CD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Atrolysin_E Atrolysin E], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.44 3.4.24.44] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KUK OCA].  

[[Category: Chiou, S H.]]

[[Category: Huang, K F.]]

[[Category: Ko, T P.]]

[[Category: Wang, A H.J.]]

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