1z8i

From Proteopedia

---

Revision as of 18:24, 12 November 2007

proteopedia linkproteopedia link

spinqualitylabelsall models 1z8i, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of the thrombin mutant G193A bound to PPACK

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The oxyanion hole of serine proteases is formed by the backbone N atoms of, the catalytic Ser-195 and Gly-193 and engages the backbone O atom of the, P1 residue of substrate in an important H-bonding interaction. The, energetic contribution of this interaction in the ground and transition, states is presently unknown. Measurements of the individual rate constants, defining the catalytic mechanism of substrate hydrolysis for wild-type, thrombin and trypsin and their G193A and G193P mutants reveal that Gly-193, is required for optimal substrate binding and acylation. Crystal, structures of the G193A and G193P mutants of thrombin bound to the active, site inhibitor H-d-Phe-Pro-Arg-CH2Cl document the extent of perturbation, induced by the replacement of Gly-193. The Ala mutant weakens the, H-bonding interaction of the N atom of residue 193, whereas the Pro, substitution abrogates it altogether with additional small shifts of the, protein backbone. From the kinetic and structural data, we estimate that, the H-bonding interaction in the oxyanion hole contributes a stabilization, of the ground and transition states of > 1.5 kcal/mol but < 3.0 kcal/mol., These results shed light on a basic aspect of the enzyme-substrate, interaction in the entire family of trypsin-like serine proteases.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1Z8I is a Protein complex structure of sequences from Homo sapiens with NAG, ZN and NA as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

Energetic and structural consequences of perturbing Gly-193 in the oxyanion hole of serine proteases., Bobofchak KM, Pineda AO, Mathews FS, Di Cera E, J Biol Chem. 2005 Jul 8;280(27):25644-50. Epub 2005 May 12. PMID:15890651

Page seeded by OCA on Mon Nov 12 20:31:01 2007