Structure-activity relationships of penem antibiotics: crystallographic structures and implications for their antimicrobial activities.
Twelve closely related crystal structures of the penem derivatives revealed a characteristic short contact of the oxygen atom in the C2 side-chains with the S1 atom. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity. In particular, the penems which show high antimicrobial activity have similar torsion angles for S1-C2-C1'-C2', suggesting that the disposition of the C2' atom would be important for binding to penicillin-interacting enzymes. Two conformations of the C6 hydroxyethyl group were observed in the crystal structures. Of those two, the conformation with a larger torsion angle (delta = 179.2 degrees) is deduced to be the enzyme-bound conformation in the Michaelis complex.
Tanaka
R
R
Suntory Ltd, Institute for Biomedical Research, Shimamoto, Osaka, Japan.
Oyama
Y
Y
Imajo
S
S
Matsuki
S
S
Ishiguro
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D015780:Carbapenems