Gazouli M, Legakis N J, Tzouvelekis L S
Department of Microbiology, Medical School, University of Athens, Greece.
FEMS Microbiol Lett. 1998 Dec 15;169(2):289-93. doi: 10.1111/j.1574-6968.1998.tb13331.x.
The effect of substitution of asparagine for arginine at position 276 (Ambler's numbering) on the properties of the extended-spectrum beta-lactamase CTX-M-4 was studied. Compared with CTX-M-4, the mutant beta-lactamase CTX-M-4(R276N) conferred lower levels of resistance to cefotaxime, ceftriaxone and aztreonam while the levels of resistance to penicillins and penicillin-inhibitor combinations were similar. Arg-276-->Asn substitution rendered CTX-M-4 slightly less susceptible to inhibition by clavulanate and tazobactam. It also caused a three-fold reduction in the relative rate of hydrolysis of cefotaxime. These results indicate that Arg-276 in CTX-M-type beta-lactamases may be implicated in hydrolysis of oxyimino-beta-lactams; they do not, however, support the hypothesis that Arg-276 is the functional equivalent of Arg-244 found in other class A beta-lactamases.
研究了在276位（安布勒编号）将精氨酸替换为天冬酰胺对超广谱β-内酰胺酶CTX-M-4性质的影响。与CTX-M-4相比，突变型β-内酰胺酶CTX-M-4（R276N）对头孢噻肟、头孢曲松和氨曲南的耐药水平较低，而对青霉素和青霉素抑制剂组合的耐药水平相似。精氨酸276位替换成天冬酰胺使CTX-M-4对克拉维酸和他唑巴坦的抑制作用稍不敏感。它还使头孢噻肟的相对水解速率降低了三倍。这些结果表明，CTX-M型β-内酰胺酶中的精氨酸276可能与氧亚氨基-β-内酰胺的水解有关；然而，它们并不支持精氨酸276与其他A类β-内酰胺酶中发现的精氨酸244功能等效的假设。
