2',3'-Dialdehydo-UDP-N-acetylglucosamine inhibits UDP-N-acetylglucosamine 2-epimerase, the key enzyme of sialic acid biosynthesis.
Sialic acids comprise a family of terminal sugars essential for a variety of biological recognition systems. UDP-N-acetylglucosamine 2-epimerase catalyzes the first step of their biosynthesis. Periodate-oxidized UDP-N-acetylglucosamine, namely 2',3'-dialdehydo-UDP-alpha-D-N-acetylglucosamine, was found to be an effective inhibitor of this enzyme, compared with the periodate oxidation products of compounds such as UDP, uridine or methyl riboside. It bound covalently to amino acids in the active site causing an irreversible inhibition. This compound may therefore represent a basis for the synthesis of potent inhibitors of UDP-N-acetylglucosamine 2-epimerase and, as a consequence, of the biosynthesis of sialic acids.
Blume
Astrid
A
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, 14195 Berlin-Dahlem, Germany.
Chen
Hao
H
Reutter
Werner
W
Schmidt
Richard R
RR
Hinderlich
Stephan
S
D000818:Animals; D002238:Carbohydrate Epimerases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010504:Periodic Acid; D012794:Sialic Acids / Q000096:biosynthesis*; D018411:Spodoptera; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry / Q000494:pharmacology*
C460841:2',3'-dialdehydro-UDP-N-acetylglucosamine; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D012794:Sialic Acids; D010504:Periodic Acid; D014537:Uridine Diphosphate N-Acetylglucosamine; C009288:metaperiodate; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase; C023223:UDP-N-acetylglucosamine 4-epimerase; C083982:wecB protein, E coli