6pik | pdb_00006pik
Tetrameric cryo-EM ArnA
Structural highlights
Function[A0A3W2RQG2_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:SAAS01095241] [A0A479JW67_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:SAAS01095241] Publication Abstract from PubMedGram-negative bacteria evade the attack of cationic antimicrobial peptides through modifying their lipid A structure in their outer membranes with 4-amino-4-deoxy-L-arabinose (Ara4N). ArnA is a crucial enzyme in the lipid A modification pathway and its deletion abolishes the polymyxin resistance of gram-negative bacteria. Previous studies by X-ray crystallography have shown that full-length ArnA forms a three-bladed propeller-shaped hexamer. Here, the structures of ArnA determined by cryo-electron microscopy (cryo-EM) reveal that ArnA exists in two 3D architectures, hexamer and tetramer. This is the first observation of a tetrameric ArnA. The hexameric cryo-EM structure is similar to previous crystal structures but shows differences in domain movements and conformational changes. We propose that ArnA oligomeric states are in a dynamic equilibrium, where the hexamer state is energetically more favorable, and its domain movements are important for cooperating with downstream enzymes in the lipid A-Ara4N modification pathway. The results provide us with new possibilities to explore inhibitors targeting ArnA. Cryo-electron microscopy structures of ArnA, a key enzyme for polymyxin resistance, revealed unexpected oligomerizations and domain movements.,Yang M, Chen YS, Ichikawa M, Calles-Garcia D, Basu K, Fakih R, Bui KH, Gehring K J Struct Biol. 2019 Jul 22. pii: S1047-8477(19)30157-1. doi:, 10.1016/j.jsb.2019.07.009. PMID:31344437[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
