Structural highlights
Function
[F4SGI5_ECOLX] Bifunctional enzyme that catalyzes the oxidative decarboxylation of UDP-glucuronic acid (UDP-GlcUA) to UDP-4-keto-arabinose (UDP-Ara4O) and the addition of a formyl group to UDP-4-amino-4-deoxy-L-arabinose (UDP-L-Ara4N) to form UDP-L-4-formamido-arabinose (UDP-L-Ara4FN). The modified arabinose is attached to lipid A and is required for resistance to polymyxin and cationic antimicrobial peptides.[HAMAP-Rule:MF_01166][SAAS:SAAS00331614]
Publication Abstract from PubMed
ArnA from Escherichia coli is a key enzyme involved in the formation of 4-amino-4-deoxy-l-arabinose. The addition of this sugar to the lipid A moiety of the lipopolysaccharide of pathogenic Gram-negative bacteria allows these organisms to evade the cationic antimicrobial peptides of the host immune system. Indeed, it is thought that such modifications may be responsible for the repeated infections of cystic fibrosis patients with Pseudomonas aeruginosa. ArnA is a bifunctional enzyme with the N- and C-terminal domains catalyzing formylation and oxidative decarboxylation reactions, respectively. The catalytically competent cofactor for the formylation reaction is N10 -formyltetrahydrofolate. Here we describe the structure of the isolated N-terminal domain of ArnA in complex with its UDP-sugar substrate and N5 -formyltetrahydrofolate. The model presented herein may prove valuable in the development of new antimicrobial therapeutics. This article is protected by copyright. All rights reserved.
Structure of the Escherichia coli ArnA N-Formyltransferase Domain in Complex with N -formyltetrahydrofolate and UDP-Ara4N.,Genthe NA, Thoden JB, Holden HM Protein Sci. 2016 May 12. doi: 10.1002/pro.2938. PMID:27171345[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Genthe NA, Thoden JB, Holden HM. Structure of the Escherichia coli ArnA N-Formyltransferase Domain in Complex with N -formyltetrahydrofolate and UDP-Ara4N. Protein Sci. 2016 May 12. doi: 10.1002/pro.2938. PMID:27171345 doi:http://dx.doi.org/10.1002/pro.2938
