亚胺培南作为β-内酰胺酶的底物和抑制剂。
Imipenem as substrate and inhibitor of beta-lactamases.
作者信息
Monks J, Waley S G
机构信息
Sir William Dunn School of Pathology, University of Oxford, U.K.
出版信息
Biochem J. 1988 Jul 15;253(2):323-8. doi: 10.1042/bj2530323.
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 degrees 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 aeruginosa; imipenem was a substrate with a low kcat. (0.8 min-1) and a low Km (0.7 microM). Possible implications for the clinical use of imipenem are considered.
研究了碳青霉烯类抗生素亚胺培南与两种代表性β-内酰胺酶之间的相互作用。第一种酶是β-内酰胺酶I，一种来自蜡样芽孢杆菌的A类β-内酰胺酶；亚胺培南表现为一种缓慢底物（在30℃和pH 7条件下，kcat为6.7 min-1，Km为0.4 mM），通过分支途径反应。在可逆反应中短暂形成了一种改变的物种；该物种可能是一种构象略有改变但稳定性大大降低的酰基酶。通过测量底物浓度和酶活性来研究反应动力学，酶活性先下降然后又更缓慢地上升。第二种酶是铜绿假单胞菌的染色体C类β-内酰胺酶；亚胺培南是一种kcat较低（0.8 min-1）且Km较低（0.7 μM）的底物。文中考虑了亚胺培南临床应用的可能影响。
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