Studying enzyme-beta-lactam interactions using X-ray diffraction.
The interaction of representative beta-lactam antibiotics with a bacterial enzyme target has been mapped in three dimensions using X-ray diffraction data to 2.25 A resolution. Examination of complexes of cephalosporin C, benzylmonobactam, and alpha-(2,3)-methylenepenicillin G with the D-alanyl-D-alanine transpeptidase-carboxypeptidase from Streptomyces R61 shows that the enzyme's reactive serine has acylated the beta-lactam ring of each inhibitor. The known half-lives of the three acyl complexes can be correlated with the distance of the drug's carboxylate (or sulfonate) group from complementary groups on the DD-peptidase.
Kelly
J A
JA
University of Connecticut, Department of Molecular and Cell Biology, Storrs.
Knox
J R
JR
Zhao
H
H
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D002511:Cephalosporins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008997:Monobactams / Q000737:chemistry / Q000378:metabolism; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000378:metabolism*; D010400:Penicillin G / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology*; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D008997:Monobactams; C054982:2,3-methylene penam; C025163:cephalosporin C; C067978:benzylmonobactam; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G