2GN9

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

Summary for 2GN9

• Entry DOI: 10.2210/pdb2gn9/pdb
• Related: 2GN4 2GN6 2GN8 2GNA
• Descriptor: UDP-GlcNAc C6 dehydratase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, URIDINE-5'-DIPHOSPHATE-GLUCOSE, ... (5 entities in total)
• Functional Keywords: rossmann fold, tyk triad, sdr, enzyme, dehydratase, udp-glcnac, nadp, lyase
• Biological source: Helicobacter pylori
• Total number of polymer chains: 2
• Total formula weight: 80264.07

Authors

Ishiyama, N.,Creuzenet, C.,Lam, J.S.,Berghuis, A.M. (deposition date: 2006-04-09, release date: 2006-05-09, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)