1br8

From Proteopedia

Revision as of 13:33, 15 February 2008

IMPLICATIONS FOR FUNCTION AND THERAPY OF A 2.9A STRUCTURE OF BINARY-COMPLEXED ANTITHROMBIN

Overview

The crystal structure of a binary complex of human antithrombin with a, peptide of the same sequence as its reactive loop (P14-P3) has been, determined at 2.9 A. The peptide binds as the middle strand s4A in the A, beta-sheet, homologously to that of the reactive loop in the latent and, cleaved forms of antithrombin. Peptide binding results in the complete, expulsion of the hinge region of the loop from the A beta-sheet although, the conformation differs from that of heparin-activated antithrombin. The, 36-fold increase in the rate of reaction of the binary complex with factor, Xa indicates that full loop expulsion alone is not sufficient for complete, heparin activation of antithrombin but that this is also dependent on the, overall conformation of the molecule. Previous studies have demonstrated, that reactive loop peptides can block or reverse the polymerisation of, serpins associated with cirrhosis and thrombosis. The antithrombin binary, complex structure defines the precise localisation of the blocking peptide, in a serpin and provides the basis for rational drug design for mimetics, that will prevent polymerisation in vivo and so ameliorate the associated, disease.

About this Structure

1BR8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Implications for function and therapy of a 2.9 A structure of binary-complexed antithrombin., Skinner R, Chang WS, Jin L, Pei X, Huntington JA, Abrahams JP, Carrell RW, Lomas DA, J Mol Biol. 1998;283(1):9-14. PMID:9761669

Page seeded by OCA on Fri Feb 15 15:33:15 2008