Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task
Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task
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DOI：
10.1073/pnas.97.8.3878
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Lerner, RA
中科院分区：
文献类型：
--
作者：
Karlstrom, A;Zhong, GF;Lerner, RA
通过用两种不同但结构相关的β-二酮半抗原免疫产生的催化醛缩酶抗体被克隆和测序，以研究独立进化的催化剂之间的相似性和差异。动力学和序列分析加上诱变，结构和建模研究表明，在这些催化剂的进化中的定义事件是一个体细胞突变，放置在一个深的赖氨酸残基，但否则未精制，疏水口袋。我们认为，共价化学可能很容易从免疫库中选择的传统的非共价相互作用，形成了免疫化学的基础，直到这个时候。此外，我们相信这些实验概括了自然界酶进化中的决定性事件，特别是当它们与化学机制、催化混杂和基因复制有关时。
Catalytic aldolase antibodies generated by immunization with two different, but structurally related, P-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.