The unusual binding mode of cnicin to the antibacterial target enzyme MurA revealed by X-ray crystallography.
We present the X-ray structure of the antibacterial target enzyme MurA in complex with its substrate UNAG and the sesquiterpene lactone cnicin, a potent inhibitor of the enzyme. The structure reveals that MurA has catalyzed the formation of a covalent adduct between cnicin and UNAG. This adduct, which can be regarded as a noncovalent suicide inhibitor, has been formed by an unusual "anti-Michael" 1,3-addition of UNAG to an alpha,beta-unsaturated carbonyl function in cnicin.
Steinbach
Anke
A
Pharmazeutische Chemie, Universität Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Scheidig
Axel J
AJ
Klein
Christian D
CD
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology; D012717:Sesquiterpenes / Q000378:metabolism*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D012717:Sesquiterpenes; D014537:Uridine Diphosphate N-Acetylglucosamine; C012849:cnicin; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase