2ch2

From Proteopedia

Revision as of 16:03, 5 November 2007

STRUCTURE OF THE ANOPHELES GAMBIAE 3-HYDROXYKYNURENINE TRANSAMINASE IN COMPLEX WITH INHIBITOR

Overview

In Anopheles gambiae, the vector for the most deadly malaria parasite, Plasmodium falciparum, xanthurenic acid (XA) plays a key role in parasite, gametogenesis and fertility. In mosquitoes, XA is produced by, transamination of 3-hydroxykynurenine (3-HK), a reaction that represents, the main route to prevent the accumulation of the potentially toxic 3-HK, excess. Interfering with XA metabolism in A. gambiae therefore appears an, attractive avenue for the development of malaria transmission-blocking, drugs and insecticides. We have determined the crystal structure of A., gambiae 3-HK transaminase in its pyridoxal 5'-phosphate form and in, complex with a newly synthesized competitive enzyme inhibitor. Structural, inspection of the enzyme active site reveals the key molecular, determinants for ligand recognition and catalysis. Major contributions, toward inhibitor binding are provided by a salt bridge between the, inhibitor carboxylate and Arg-356 and by a remarkable hydrogen bond, network involving the anthranilic moiety of the inhibitor and backbone, atoms of residues Gly-25 and Asn-44. This study may be useful for the, structure-based design of specific enzyme inhibitors of potential interest, as antimalarial agents.

About this Structure

2CH2 is a Single protein structure of sequence from Anopheles gambiae with KY1, LLP and KY1 as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase., Rossi F, Garavaglia S, Giovenzana GB, Arca B, Li J, Rizzi M, Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5711-6. Epub 2006 Apr 3. PMID:16585514

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