2BLN

N-terminal formyltransferase domain of ArnA in complex with N-5- formyltetrahydrofolate and UMP

2BLN の概要

• エントリーDOI: 10.2210/pdb2bln/pdb
• 関連するPDBエントリー: 1U9J 2BLL
• 分子名称: PROTEIN YFBG, N-{[4-({[(6R)-2-amino-5-formyl-4-oxo-1,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]carbonyl}-L-glutamic acid, URIDINE-5'-MONOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: transferase, formyltransferase, l-ara4n biosynthesis, methyltransferase
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68205.33

構造登録者

Williams, G.J.,Breazeale, S.D.,Raetz, C.R.H.,Naismith, J.H. (登録日: 2005-03-07, 公開日: 2005-04-08, 最終更新日: 2024-05-08)

主引用文献

Williams, G.J.,Breazeale, S.D.,Raetz, C.R.H.,Naismith, J.H.
Structure and Function of Both Domains of Arna, a Dual Function Decarboxylase and a Formyltransferase, Involved in 4-Amino-4-Deoxy-L-Arabinose Biosynthesis.
J.Biol.Chem., 280:23000-, 2005

PubMed Abstract: Modification of the lipid A moiety of lipopolysaccharide by the addition of the sugar 4-amino-4-deoxy-L-arabinose (L-Ara4N) is a strategy adopted by pathogenic Gram-negative bacteria to evade cationic antimicrobial peptides produced by the innate immune system. L-Ara4N biosynthesis is therefore a potential anti-infective target, because inhibiting its synthesis would render certain pathogens more sensitive to the immune system. The bifunctional enzyme ArnA, which is required for L-Ara4N biosynthesis, catalyzes the NAD(+)-dependent oxidative decarboxylation of UDP-glucuronic acid to generate a UDP-4'-keto-pentose sugar and also catalyzes transfer of a formyl group from N-10-formyltetrahydrofolate to the 4'-amine of UDP-L-Ara4N. We now report the crystal structure of the N-terminal formyltransferase domain in a complex with uridine monophosphate and N-5-formyltetrahydrofolate. Using this structure, we identify the active site of formyltransfer in ArnA, including the key catalytic residues Asn(102), His(104), and Asp(140). Additionally, we have shown that residues Ser(433) and Glu(434) of the decarboxylase domain are required for the oxidative decarboxylation of UDP-GlcUA. An E434Q mutant is inactive, suggesting that chemical rather than steric properties of this residue are crucial in the decarboxylation reaction. Our data suggest that the decarboxylase domain catalyzes both hydride abstraction (oxidation) from the C-4' position and the subsequent decarboxylation.

PubMed: 15809294
DOI: 10.1074/JBC.M501534200

実験手法

X-RAY DIFFRACTION (1.2 Å)