An enzyme-substrate complex involved in bacterial cell wall biosynthesis.
The crystal structure of UDP-N-acetylenolpyruvylglucosamine reductase in the presence of its substrate, enolpyruvyl-UDP-N-acetylglucosamine, has been solved to 2.7 A resolution. This enzyme is responsible for the synthesis of UDP-N-acetylmuramic acid in bacterial cell wall biosynthesis and consequently provides an attractive target for the design of antibacterial agents. The structure reveals a novel flavin binding motif, shows a striking alignment of the flavin with the substrate, and suggests a catalytic mechanism for the reduction of this unusual enol ether.
Benson
T E
TE
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Filman
D J
DJ
Walsh
C T
CT
Hogle
J M
JM
D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry; D001665:Binding Sites; D002237:Carbohydrate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D010728:Phosphoenolpyruvate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000737:chemistry / Q000378:metabolism
D000890:Anti-Infective Agents; D008024:Ligands; D014538:Uridine Diphosphate N-Acetylmuramic Acid; D005182:Flavin-Adenine Dinucleotide; D014537:Uridine Diphosphate N-Acetylglucosamine; C038277:UDP-N-acetylglucosamine-enolpyruvate; D010728:Phosphoenolpyruvate; D002237:Carbohydrate Dehydrogenases; C023215:UDP-N-acetylmuramate dehydrogenase