1Z7E

Crystal structure of full length ArnA

1Z7E の概要

• エントリーDOI: 10.2210/pdb1z7e/pdb
• 関連するPDBエントリー: 1Z73 1Z74 1Z75 1Z7B
• 分子名称: protein ArnA, ADENOSINE-5'-TRIPHOSPHATE, URIDINE-5'-DIPHOSPHATE-GLUCURONIC ACID (3 entities in total)
• 機能のキーワード: rossmann fold; ob-like fold, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 452839.43

構造登録者

Gatzeva-Topalova, P.Z.,May, A.P.,Sousa, M.C. (登録日: 2005-03-24, 公開日: 2005-06-07, 最終更新日: 2023-08-23)

主引用文献

Gatzeva-Topalova, P.Z.,May, A.P.,Sousa, M.C.
Structure and Mechanism of ArnA: Conformational Change Implies Ordered Dehydrogenase Mechanism in Key Enzyme for Polymyxin Resistance
Structure, 13:929-942, 2005

PubMed Abstract: The modification of lipid A with 4-amino-4-deoxy-L-arabinose (Ara4N) allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-Glucuronic acid (UDP-GlcA), and a transformylase domain that formylates UDP-Ara4N. Here, we describe the crystal structure of the full-length bifunctional ArnA with UDP-GlcA and ATP bound to the dehydrogenase domain. Binding of UDP-GlcA triggers a 17 A conformational change in ArnA_DH that opens the NAD+ binding site while trapping UDP-GlcA. We propose an ordered mechanism of substrate binding and product release. Mutation of residues R619 and S433 demonstrates their importance in catalysis and suggests that R619 functions as a general acid in catalysis. The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors.

PubMed: 15939024
DOI: 10.1016/j.str.2005.03.018

実験手法

X-RAY DIFFRACTION (3 Å)