2bl1

From Proteopedia

Revision as of 15:36, 5 November 2007

CRYSTAL STRUCTURE OF A PUTATIVE PHOSPHINOTHRICIN ACETYLTRANSFERASE (PA4866) FROM PSEUDOMONAS AERUGINOSA PAC1

Overview

Modification of the lipid A moiety of lipopolysaccharide by the addition, of the sugar 4-amino-4-deoxy-L-arabinose (L-Ara4N) is a strategy adopted, by pathogenic Gram-negative bacteria to evade cationic antimicrobial, peptides produced by the innate immune system. L-Ara4N biosynthesis is, therefore a potential anti-infective target, because inhibiting its, synthesis would render certain pathogens more sensitive to the immune, system. The bifunctional enzyme ArnA, which is required for L-Ara4N, biosynthesis, catalyzes the NAD(+)-dependent oxidative decarboxylation of, UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also, catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to, the 4'-amine of UDP-L-Ara4N. We now report the crystal structure of the, N-terminal formyltransferase domain in a complex with uridine, monophosphate and N-5-formyltetrahydrofolate. Using this structure, we, identify the active site of formyltransfer in ArnA, including the key, catalytic residues Asn(102), His(104), and Asp(140). Additionally, we have, shown that residues Ser(433) and Glu(434) of the decarboxylase domain are, required for the oxidative decarboxylation of UDP-GlcUA. An E434Q mutant, is inactive, suggesting that chemical rather than steric properties of, this residue are crucial in the decarboxylation reaction. Our data suggest, that the decarboxylase domain catalyzes both hydride abstraction, (oxidation) from the C-4' position and the subsequent decarboxylation.

About this Structure

2BL1 is a Single protein structure of sequence from Pseudomonas aeruginosa with AZI, SO4 and GOL as ligands. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

Reference

Structure and function of both domains of ArnA, a dual function decarboxylase and a formyltransferase, involved in 4-amino-4-deoxy-L-arabinose biosynthesis., Williams GJ, Breazeale SD, Raetz CR, Naismith JH, J Biol Chem. 2005 Jun 17;280(24):23000-8. Epub 2005 Apr 4. PMID:15809294

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