1KUI

Crystal Structure of a Taiwan Habu Venom Metalloproteinase complexed with pEQW.

Summary for 1KUI

• Entry DOI: 10.2210/pdb1kui/pdb
• Related: 1KUF 1KUG 1KUK
• Descriptor: metalloproteinase, EQW, CADMIUM ION, ... (4 entities in total)
• Functional Keywords: alpha/beta protein, retro-binding manner, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Protobothrops mucrosquamatus; More
• Total number of polymer chains: 2
• Total formula weight: 24946.37

Authors

Huang, K.F.,Chiou, S.H.,Ko, T.P.,Wang, A.H.J. (deposition date: 2002-01-22, release date: 2002-07-10, Last modification date: 2024-10-23)

Primary citation

Huang, K.F.,Chiou, S.H.,Ko, T.P.,Wang, A.H.
Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor analogues.
Eur.J.Biochem., 269:3047-3056, 2002

PubMed Abstract: 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.

PubMed: 12071970
DOI: 10.1046/j.1432-1033.2002.02982.x

Experimental method

X-RAY DIFFRACTION (1.5 Å)