1u9j

From Proteopedia

Revision as of 01:49, 21 November 2007

Crystal Structure of E. coli ArnA (PmrI) Decarboxylase Domain

Overview

Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa can modify the structure of lipid A in their, outer membrane with 4-amino-4-deoxy-l-arabinose (Ara4N). Such modification, results in resistance to cationic antimicrobial peptides of the innate, immune system and antibiotics such as polymyxin. ArnA is a key enzyme in, the lipid A modification pathway, and its deletion abolishes both the, Ara4N-lipid A modification and polymyxin resistance. ArnA is a, bifunctional enzyme. It can catalyze (i) the NAD(+)-dependent, decarboxylation of UDP-glucuronic acid to UDP-4-keto-arabinose and (ii), the N-10-formyltetrahydrofolate-dependent formylation of, UDP-4-amino-4-deoxy-l-arabinose. We show that the NAD(+)-dependent, decarboxylating activity is contained in the 360 amino acid C-terminal, domain of ArnA. This domain is separable from the N-terminal fragment, and, its activity is identical to that of the full-length enzyme. The crystal, structure of the ArnA decarboxylase domain from E. coli is presented here., The structure confirms that the enzyme belongs to the short-chain, dehydrogenase/reductase (SDR) family. On the basis of sequence and, structure comparisons of the ArnA decarboxylase domain with other members, of the short-chain dehydrogenase/reductase (SDR) family, we propose a, binding model for NAD(+) and UDP-glucuronic acid and the involvement of, residues T(432), Y(463), K(467), R(619), and S(433) in the mechanism of, NAD(+)-dependent oxidation of the 4-OH of the UDP-glucuronic acid and, decarboxylation of the UDP-4-keto-glucuronic acid intermediate.

About this Structure

1U9J is a Single protein structure of sequence from Escherichia coli with SO4 as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of Escherichia coli ArnA (PmrI) decarboxylase domain. A key enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance., Gatzeva-Topalova PZ, May AP, Sousa MC, Biochemistry. 2004 Oct 26;43(42):13370-9. PMID:15491143

Page seeded by OCA on Wed Nov 21 03:56:33 2007