1kug

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[[Image:1kug.jpg|left|200px]]<br /><applet load="1kug" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1kug.jpg|left|200px]]
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caption="1kug, resolution 1.37&Aring;" />
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'''Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW'''<br />
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{{Structure
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|PDB= 1kug |SIZE=350|CAPTION= <scene name='initialview01'>1kug</scene>, resolution 1.37&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CD:CADMIUM ION'>CD</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with its endogenous inhibitor pENW'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1KUG 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=1KUG OCA].
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1KUG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Protobothrops_mucrosquamatus Protobothrops mucrosquamatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KUG OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12071970 12071970]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/12071970 12071970]
[[Category: Atrolysin E]]
[[Category: Atrolysin E]]
[[Category: Protobothrops mucrosquamatus]]
[[Category: Protobothrops mucrosquamatus]]
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[[Category: retro-binding manner]]
[[Category: retro-binding manner]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:38:01 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:22:23 2008''

Revision as of 10:22, 20 March 2008


PDB ID 1kug

Drag the structure with the mouse to rotate
, resolution 1.37Å
Ligands:
Activity: Atrolysin E, with EC number 3.4.24.44
Coordinates: save as pdb, mmCIF, xml



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

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