白色链霉菌G丝氨酸β-内酰胺酶。通过突变酶的分子建模探究催化机制。
Streptomyces albus G serine beta-lactamase. Probing of the catalytic mechanism via molecular modelling of mutant enzymes.
作者信息
Lamotte-Brasseur J, Jacob-Dubuisson F, Dive G, Frère J M, Ghuysen J M
机构信息
Centre d'Ingénierie des Protéines, Université de Liège, Sart tilman, Belgium.
出版信息
Biochem J. 1992 Feb 15;282 ( Pt 1)(Pt 1):189-95. doi: 10.1042/bj2820189.
Abstract
In previous studies, several amino acids of the active site of class A beta-lactamases have been modified by site-directed mutagenesis. On the basis of the catalytic mechanism proposed for the Streptomyces albus G beta-lactamase [Lamotte-Brasseur, Dive, Dideberg, Charlier, Frère & Ghuysen (1991) Biochem. J. 279, 213-221], the influence that these mutations exert on the hydrogen-bonding network of the active site has been analysed by molecular mechanics. The results satisfactorily explain the effects of the mutations on the kinetic parameters of the enzyme's activity towards a set of substrates. The present study also shows that, upon binding a properly structured beta-lactam compound, the impaired cavity of a mutant enzyme can readopt a functional hydrogen-bonding-network configuration.
摘要
在先前的研究中，通过定点诱变对A类β-内酰胺酶活性位点的几种氨基酸进行了修饰。基于为白色链霉菌Gβ-内酰胺酶提出的催化机制[拉莫特-布拉瑟尔、迪夫、迪德伯格、沙利耶、弗雷尔和居伊森（1991年）《生物化学杂志》279卷，213 - 221页]，通过分子力学分析了这些突变对活性位点氢键网络的影响。结果令人满意地解释了这些突变对该酶针对一组底物的活性动力学参数的影响。本研究还表明，在结合结构合适的β-内酰胺化合物时，突变酶受损的腔可以重新采用功能性氢键网络构型。
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