IMIPENEM AS SUBSTRATE AND INHIBITOR OF BETA-LACTAMASES
IMIPENEM AS SUBSTRATE AND INHIBITOR OF BETA-LACTAMASES
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DOI：
10.1042/bj2530323
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发表时间：
1988-07-15
影响因子：
4.1
通讯作者：
WALEY, SG
中科院分区：
文献类型：
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作者：
MONKS, J;WALEY, SG
碳青霉烯类抗生素亚胺培南与两种代表性β-内酰胺类抗生素之间的相互作用已经研究了内酰胺酶。第一种酶是β-内酰胺酶I，A类β-来自蜡状芽孢杆菌的内酰胺酶;亚胺培南表现为慢底物（kcat. 6.7 min-1，Km 0.4mM，30 ℃。C和pH 7），其通过分支途径反应。在可逆反应中形成的改变的物种是瞬时形成的;这种物种可能是一种酰基酶，其构象略有改变，但相当不稳定。通过测量底物浓度和酶活性来研究反应的动力学，酶活性下降，然后缓慢地再次上升。第二种酶是染色体C类β-内酰胺酶来自铜绿假单胞菌;亚胺培南是具有低kcat的底物。(0.8 min-1）和低Km（0.7 μ M）。亚胺培南的临床使用可能的影响被认为是。
The interaction between imipenem, a carbapenem antibiotic, and two representative .beta.-lactamases has been studied. The first enzyme was .beta.-lactamase I, a class-A .beta.-lactamase from Bacillus cereus; imipenem behaved as a slow substrate (kcat. 6.7 min-1, Km 0.4 mM at 30.degree. C and at pH 7) that reacted by a branched pathway. There was transient formation of an altered species formed in a reversible reaction; this species was probably an acyl-enzyme in a slightly altered, but considerably more labile, conformation. The kinetics of the reaction were investigated by measuring both the concentration of the substrate and the activity of the enzyme, which fell and then rose again more slowly. The second enzyme was the chromosomal class-C .beta.-lactamase from Pseudomonas aeurginosa; imipenem was a substrate with a low kcat. (0.8 min-1) and a low Km (0.7 .mu.M). Possible implications for the clinical use of imipenem are considered.