1u9j
From Proteopedia
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'''Crystal Structure of E. coli ArnA (PmrI) Decarboxylase Domain''' | '''Crystal Structure of E. coli ArnA (PmrI) Decarboxylase Domain''' | ||
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[[Category: May, A P.]] | [[Category: May, A P.]] | ||
[[Category: Sousa, M C.]] | [[Category: Sousa, M C.]] | ||
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| - | [[Category: | + | [[Category: E coli proteome]] |
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:56:08 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:56, 3 May 2008
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. 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 Sat May 3 10:56:08 2008
