6PIK

Tetrameric cryo-EM ArnA

6PIK の概要

• エントリーDOI: 10.2210/pdb6pik/pdb
• EMDBエントリー: 20352
• 分子名称: Bifunctional polymyxin resistance protein ArnA, UDP-4-amino-4-deoxy-L-arabinose formyltransferase (2 entities in total)
• 機能のキーワード: polymyxin resistance, hexamer, tetramer, antibiotic
• 由来する生物種: Escherichia coli DH5[alpha]; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 291100.01

構造登録者

Yang, M.,Gehring, K. (登録日: 2019-06-26, 公開日: 2019-07-31, 最終更新日: 2024-03-20)

主引用文献

Yang, M.,Chen, Y.S.,Ichikawa, M.,Calles-Garcia, D.,Basu, K.,Fakih, R.,Bui, K.H.,Gehring, K.
Cryo-electron microscopy structures of ArnA, a key enzyme for polymyxin resistance, revealed unexpected oligomerizations and domain movements.
J.Struct.Biol., 208:43-50, 2019

PubMed Abstract: Gram-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.

PubMed: 31344437
DOI: 10.1016/j.jsb.2019.07.009

実験手法

ELECTRON MICROSCOPY (7.8 Å)