Class C beta-lactamases

M. Galleni, G. Amicosante, J. M. Frere, A Survey of the Kinetic Parameters of Class C beta-Lactamases. Cephalosporins and Other beta-Lactam Compounds , Biochem. J. 1988, 255, 123-129. 

Structure of Citrobacter freundii Class C Beta-Lactamase... 

This experimental result offers a convincing rationalization for the slow deacylation of aztreonam in class C beta-lactamases. 

The reaction with class C beta-lactamases was typically biphasic, reflecting two kinetically distinct conformations of the protein [10,13]. 

The stability of the acyl-enzyme complexes formed with C freundii class C beta-lactamase allowed solution of their structures by X-ray crystallography (Fig. 8). No significant changes in protein structure occurred, except that the side chain of Aspl23 moved to accommodate... 

Crichlow GV, Nukaga M, Doppalapudi VR. et al Inhibition of class c beta-lactamases Structure of a re-... 

Hermann JC, C Hensen, L Ridder, AJ Mulholland, H-D Holtje (2005) Mechanisms of antibiotic resistance QM/MM modeling of the acylation reaction of a class A beta-lactamase with benzylpeni-cillin. J. Am. Chem. Soc. 127 (12) 44544465... 

Inspection of class A beta-lactamase crystal structures indicated that a water molecule in an equivalent position would be much less activated because there is a serine residue replacing the tyrosine of class C enzymes [7,11]. Attack in a class A enzyme occurs from the opposite side of the ester, with activation of the water molecule occurring through an extension of the hydrogen bond network that is not present in class C enzymes. Hence, rotation about C3-C4 is less critical to the mechanism of deacylation in these enzymes and restricting the rotation should have less impact on the stability of the acyl-enzyme complex. 

Several classes of (3-lactamases, often encoded in transmissible plasmids, have spread worldwide rapidly among bacteria, seriously decreasing the effectivenss of penicillins and other (3-lactam anti-biotics.t y Most (3-lactamases (classes A and C) contain an active site serine and are thought to have evolved from the dd transpeptidases, but the B typey has a catalytic Zn2+. The latter, as well as a recently discovered type A enzyme,2 hydrolyze imipenem, currently one of the antibiotics of last resort used to treat infections by penicillin-resistant bacteria. Some (3-lactam antibiotics are also powerful inhibitors of (3-lactamases.U/aa/bb These antibiotics may also have uses in inhibition of serine proteasesCC/dd such as elastase. Some antibiotic-resistant staphylococci produce an extra penicillin-binding protein that protects them from beta lactams.ee Because of antibiotic resistance the isolation of antibiotics from mixed populations of microbes from soil, swamps, and lakes continues. Renewed efforts are being... 

Sanschagrin, F., Levesque, R. C. (2005). A specific peptide inhibitor of the class B metallo-beta-lactamase L-1 from Stenotrophomonas maltophilia identified using phage display. J. Antimicrob. Chemother., 55, 252-255. 

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