Structural and kinetic evidence for strain in biological catalysis.
Structural and kinetic evidence for strain in biological catalysis.
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DOI：
10.1021/bi981578c
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发表时间：
1998-10
期刊：
影响因子：
2.9
通讯作者：
F. Romesberg;B. Santarsiero;B. Spiller;J. Yin;D. Barnes;P. Schultz;R. Stevens
中科院分区：
文献类型：
--
作者：
F. Romesberg;B. Santarsiero;B. Spiller;J. Yin;D. Barnes;P. Schultz;R. Stevens
酶催化的一个经典假说是底物中应变的诱导。这一概念首先由Halfman用锁和钥匙的类比来表达-“钥匙并不完全适合锁，但会对锁产生一定的张力”（1）。这种机制经常被用来解释酶的催化效率，但很难最终确定（2-7）。在这里，我们描述的抗体金属螯合酶的X射线晶体学和突变的研究，强烈支持的概念，这种抗体催化金属离子插入到卟啉环诱导应变。种系前体的分析表明，这种应变机制出现在响应于构象扭曲的N-烷基中卟啉的亲和力成熟的过程中。
A classic hypothesis for enzyme catalysis is the induction of strain in the substrate. This notion was first expressed by Haldane with the lock and key analogy-"the key does not fit the lock perfectly but exercises a certain strain on it" (1). This mechanism has often been invoked to explain the catalytic efficiency of enzymes but has been difficult to establish conclusively (2-7). Here we describe X-ray crystallographic and mutational studies of an antibody metal chelatase which strongly support the notion that this antibody catalyzes metal ion insertion into the porphyrin ring by inducing strain. Analysis of the germline precursor suggests that this strain mechanism arose during the process of affinity maturation in response to a conformationally distorted N-alkylmesoporphyrin.