Raquet X, Lamotte-Brasseur J, Fonzé E, Goussard S, Courvalin P, Frère J M
Centre d'Ingénierie des Protéines, Université de Liege, Sart-Tilman, Belgium.
J Mol Biol. 1994 Dec 16;244(5):625-39. doi: 10.1006/jmbi.1994.1756.
The catalytic properties of six "natural" mutants of the TEM-1 beta-lactamase have been studied in detail, with special emphasis on their activity versus third-generation cephalosporins. On the basis of the recently determined high-resolution structure of the wild-type enzyme, and of the substrates' structures optimized by the AMI quantum chemistry method, we have attempted to explain the influences of the mutations on the substrate profiles of the enzymes. Some of the kinetic results have thus received a satisfactory, semi-quantitative interpretation, especially in the case of single mutations. Analysis of the double mutants proved more hazardous. Extending the comparison to some other class A beta-lactamases showed that similar properties could result from different sequences, supplying an interesting example of convergent evolution within a generally diverging family.
已对TEM-1β-内酰胺酶的六个“天然”突变体的催化特性进行了详细研究，特别强调了它们对第三代头孢菌素的活性。基于最近确定的野生型酶的高分辨率结构以及通过AMI量子化学方法优化的底物结构，我们试图解释突变对酶底物谱的影响。因此，一些动力学结果得到了令人满意的半定量解释，特别是在单突变的情况下。对双突变体的分析证明更具挑战性。将比较扩展到其他一些A类β-内酰胺酶表明，不同的序列可能导致相似的特性，这为一个普遍分化的家族内的趋同进化提供了一个有趣的例子。
