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• W1985035265 abstract "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 T432, Y463, K467, R619, and S433 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." @default.
• W1985035265 created "2016-06-24" @default.
• W1985035265 creator A5013562820 @default.
• W1985035265 creator A5053398061 @default.
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• W1985035265 date "2004-09-30" @default.
• W1985035265 modified "2023-10-18" @default.
• W1985035265 title "Crystal Structure of <i>Escherichia coli</i> ArnA (PmrI) Decarboxylase Domain. A Key Enzyme for Lipid A Modification with 4-Amino-4-deoxy-<scp>l</scp>-arabinose and Polymyxin Resistance^," @default.
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• W1985035265 doi "https://doi.org/10.1021/bi048551f" @default.
• W1985035265 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2680612" @default.
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