CRITICAL HYDROGEN-BONDING BY SERINE 235 FOR CEPHALOSPORINASE ACTIVITY OF TEM-1 BETA-LACTAMASE
CRITICAL HYDROGEN-BONDING BY SERINE 235 FOR CEPHALOSPORINASE ACTIVITY OF TEM-1 BETA-LACTAMASE
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DOI：
10.1128/aac.37.11.2438
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发表时间：
1993-11-01
影响因子：
4.9
通讯作者：
MOBASHERY, S
中科院分区：
文献类型：
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作者：
IMTIAZ, U;MANAVATHU, EK;MOBASHERY, S
Ser-235在TEM-1 β-内酰胺酶的催化机制中的作用已经通过对其中Ser-235被丙氨酸取代的突变酶（Ala-235突变酶）的研究来探索。野生型和Ala-235 TEM-1酶的比较动力学分析显示，这种取代残基235对青霉素的营业额影响不大，但对头孢菌素的营业额影响较大。携带野生型TEM-1 β-内酰胺酶和Ala-235突变酶的大肠杆菌菌株的敏感性试验显示，突变的影响与酶学研究中观察到的相似。两种代表性头孢菌素对含突变酶菌株的MIC远低于携带野生型TEM-1 β-内酰胺酶的同基因菌株。另一方面，具有突变酶的菌株仍然对青霉素具有高度抗性。
The role of Ser-235 in the catalytic mechanism of the TEM-1 beta-lactamase has been explored by the study of a mutant enzyme in which Ser-235 has been substituted by alanine (Ala-235 mutant enzyme). A comparative kinetic analysis of both the wild-type and the Ala-235 TEM-1 enzymes revealed little effect of this substitution of residue 235 on the turnover of penicillins but a greater effect on the turnover of cephalosporins. Susceptibility testing of Escherichia coli strains harboring the wild-type TEM-1 beta-lactamase and the Ala-235 mutant enzyme revealed an effect of the mutation similar to that observed in the enzymological studies. The MICs of two representative cephalosporins for the strain containing the mutant enzyme were much lower than those for the isogenic strain bearing the wild-type TEM-1 beta-lactamase. On the other hand, the strain with the mutant enzyme was still highly resistant to penicillins.