Valentina Di Francescovdifrancesco@niaid.nih.gov
Beta-lactamases are enzymes produced by some Gram-negative and Gram-positive bacteria and are responsible for resistance to a broad class of-beta-lactam antibiotics, including penicillin. There are several groups and classes of beta-lactamases that result in antibiotic resistance. For example, several class C beta-lactamases result in cephalosporin resistance and some class A beta-lactamases confer resistance to oxyimino-cephalosporins, cephamycins and carbapenems.
Two different beta – lactamase structures have recently been determined by the Center for Structural Genomics of Infectious Diseases. The first AmpH enzyme is from Yersinia pestis, the causative agent of plague, and is related to the class C (AmpC) beta-lactamases, which are produced by bacteria such as Escherichia coli. Despite only 24-25% sequence homology, the structures are quite similar as can be seen by superimposing the AmpH structure (shown in orange, PDB ID:3OZH) with that of the E. coli Amp C structure (shown in green, PDB ID:1KDS). The Amp C structure has the inhibitor 3-nitrophenylboronic acid in its active site (depicted as a blue stick).
The second beta-lactamase structure determined is from Francissela tularensis, the causative agent of tularemia. Shown in orange below, the class A enzyme (subsp. tularensis SCHUS4,PDBID:3P09),is strikingly similar to that of class A carbapenemases, which confer resistance to oxyimino-cephalosporins, cephamycins and carbapenems. It is shown superimposed on 6 alpha-(hydroxypropyl) penicillate acylated NMC-A carbapenemase structure (shown in purple, the inhibitor shown in blue, PDBID:1BUL)
Last Updated March 02, 2011
Last Reviewed December 07, 2010