2GN4

Crystal structure of UDP-GlcNAc inverting 4,6-dehydratase in complex with NADPH and UDP-GlcNAc

2GN4 の概要

• エントリーDOI: 10.2210/pdb2gn4/pdb
• 関連するPDBエントリー: 2GN6
• 分子名称: UDP-GlcNAc C6 dehydratase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE, ... (5 entities in total)
• 機能のキーワード: rossmann fold, tyk triad, sdr, enzyme, dehydratase, udp-glcnac, nadp, nadph, lyase
• 由来する生物種: Helicobacter pylori
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80545.45

構造登録者

Ishiyama, N.,Creuzenet, C.,Lam, J.S.,Berghuis, A.M. (登録日: 2006-04-09, 公開日: 2006-05-09, 最終更新日: 2023-08-30)

主引用文献

Ishiyama, N.,Creuzenet, C.,Miller, W.L.,Demendi, M.,Anderson, E.M.,Harauz, G.,Lam, J.S.,Berghuis, A.M.
Structural Studies of FlaA1 from Helicobacter pylori Reveal the Mechanism for Inverting 4,6-Dehydratase Activity.
J.Biol.Chem., 281:24489-24495, 2006

PubMed Abstract: FlaA1 from the human pathogen Helicobacter pylori is an enzyme involved in saccharide biosynthesis that has been shown to be essential for pathogenicity. Here we present five crystal structures of FlaA1 in the presence of substrate, inhibitors, and bound cofactor, with resolutions ranging from 2.8 to 1.9 A. These structures reveal that the enzyme is a novel member of the short-chain dehydrogenase/reductase superfamily. Additional electron microscopy studies show the enzyme to possess a hexameric doughnut-shaped quaternary structure. NMR analyses of "real time" enzyme-substrate reactions indicate that FlaA1 is a UDP-GlcNAc-inverting 4,6-dehydratase, suggesting that the enzyme catalyzes the first step in the biosynthetic pathway of a pseudaminic acid derivative, which is implicated in protein glycosylation. Guided by evidence from site-directed mutagenesis and computational simulations, a three-step reaction mechanism is proposed that involves Lys-133 functioning as both a catalytic acid and base.

PubMed: 16651261
DOI: 10.1074/jbc.M602393200

実験手法

X-RAY DIFFRACTION (1.9 Å)