Collatz E, Labia R, Gutmann L
Laboratoire de Microbiologie Médicale, Université Paris VI, France.
Mol Microbiol. 1990 Oct;4(10):1615-20. doi: 10.1111/j.1365-2958.1990.tb00537.x.
Production of beta-lactamases, and of the plasmid-encoded TEM- and SHV-type enzymes in particular, is the most common mechanism of resistance against beta-lactam antibiotics in Gram-negative bacteria. The two ubiquitous types of enzyme have a large spectrum of activity and preferentially hydrolyse the penicillins as well as some first- and second-generation cephalosporins. Recently, point mutations in the corresponding genes have been observed, apparently selected for, in the clinical setting, by originally 'beta-lactamase-stable' third-generation cephalosporins or by monobactams, which fall into the substrate range of the mutant or 'extended-spectrum' beta-lactamases. The point mutations are clustered in three areas, each adjacent to one of the seven evolutionarily conserved boxes described by Joris et al. (1988). The substituted amino acids at positions 102 (adjacent to the alpha-3 helix), 162 (adjacent to the alpha-7 helix) and 235, 236 and 237 (on the beta-3 strand) are located in close proximity to the active-site cavity and are thought to open up novel enzyme-substrate interactions, involving, in particular, the oxyimino moieties of the newer beta-lactam compounds.
产生β-内酰胺酶，尤其是质粒编码的TEM型和SHV型酶，是革兰氏阴性菌对β-内酰胺抗生素产生耐药性的最常见机制。这两种普遍存在的酶具有广泛的活性谱，优先水解青霉素以及一些第一代和第二代头孢菌素。最近，在临床环境中观察到相应基因中的点突变，显然是由最初“对β-内酰胺酶稳定”的第三代头孢菌素或单环β-内酰胺类抗生素选择的，这些抗生素属于突变型或“超广谱”β-内酰胺酶的底物范围。点突变聚集在三个区域，每个区域与Joris等人（1988年）描述的七个进化保守框之一相邻。位于102位（与α-3螺旋相邻）、162位（与α-7螺旋相邻）以及235、236和237位（在β-3链上）的取代氨基酸紧邻活性位点腔，被认为会形成新的酶-底物相互作用，特别是涉及新型β-内酰胺化合物的肟基部分。
