期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1997
卷号：94
期号：2
页码：443-447
DOI：10.1073/pnas.94.2.443
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：{beta}-Lactamases are the primary cause of {beta}-lactam antibiotic resistance in many pathogenic organisms. The {beta}-lactamase catalytic mechanism has been shown to involve a covalent acyl-enzyme. Examination of the structure of the class A {beta}-lactamase from Bacillus licheniformis suggested that replacement of Asn-170 by leucine would disrupt the deacylation reaction by displacing the hydrolytic water molecule. When N170L {beta}-lactamase was reacted with penicillins, a novel product was formed. We postulate that with leucine at position 170 the acyl-enzyme undergoes deacylation by an intramolecular rearrangement (rather than hydrolysis) to form a thiazolidine-oxazolinone as the initial product. The oxazolinone subsequently undergoes rapid breakdown leading to the formation of N-phenylacetylglycine and N-formylpenicillamine. This appears to be the first reported case where a point mutation leads to a change in enzyme mechanism resulting in a substantially altered product, effectively changing the product specificity of {beta}-lactamase into that of D-Ala-D-Ala-carboxypeptidase interacting with benzylpenicillin.
