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ABSTRACT: 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.
Journal of Medicinal Chemistry 09/2008; 51(16):5143-7. · 5.61 Impact Factor