1kye

From Proteopedia

Revision as of 15:49, 12 November 2007

Factor Xa in complex with (R)-2-(3-adamantan-1-yl-ureido)-3-(3-carbamimidoyl-phenyl)-N-phenethyl-propionamide

Overview

A putative non-substrate like binding mode of (R)-3-amidinophenylalanine, derivatives to factor Xa, as derived from modeling experiments based on, X-ray analysis of their complexes with trypsin, was used to design a new, generation of inhibitors. However, the resulting inhibitory potencies were, not at all consistent with the working assumption, although with an, adamantyl-ureido derivative of (R)-3-amidinophenylalanine phenetyl amide a, highly selective nanomolar inhibition of factor Xa was achieved. The X-ray, analysis of the complex of this ligand with factor Xa revealed an, unexpected new binding mode, of which the most important feature is the, interaction of the C-terminal aryl moiety with a hydrophobic subregion of, the S1 subsite, while the adamantyl group occupies the hydrophobic S3/S4, subsites of the enzyme.

Disease

Known disease associated with this structure: Factor X deficiency OMIM:[227600]

About this Structure

1KYE is a Protein complex structure of sequences from Homo sapiens with CA and RUP as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.

Reference

(R)-3-Amidinophenylalanine-derived inhibitors of factor Xa with a novel active-site binding mode., Mueller MM, Sperl S, Sturzebecher J, Bode W, Moroder L, Biol Chem. 2002 Jul-Aug;383(7-8):1185-91. PMID:12437104

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