Todd Annabel E, Orengo Christine A, Thornton Janet M
Biochemistry and Molecular Biology Department, University College London, United Kingdom.
Structure. 2002 Oct;10(10):1435-51. doi: 10.1016/s0969-2126(02)00861-4.
To improve our understanding of the evolution of novel functions, we performed a sequence, structural, and functional analysis of homologous enzymes and nonenzymes of known three-dimensional structure. In most examples identified, the nonenzyme is derived from an ancestral catalytic precursor (as opposed to the reverse evolutionary scenario, nonenzyme to enzyme), and the active site pocket has been disrupted in some way, owing to the substitution of critical catalytic residues and/or steric interactions that impede substrate binding and catalysis. Pairwise sequence identity is typically insignificant, and almost one-half of the enzyme and nonenzyme pairs do not share any similarity in function. Heterooligomeric enzymes comprising homologous subunits in which one chain is catalytically inactive and enzyme polypeptides that contain internal catalytic and noncatalytic duplications of an ancient enzyme domain are also discussed.
为了增进我们对新功能进化的理解，我们对已知三维结构的同源酶和非酶进行了序列、结构和功能分析。在大多数已鉴定的例子中，非酶源自祖先催化前体（与相反的进化情况，即从非酶到酶相反），并且活性位点口袋由于关键催化残基的取代和/或阻碍底物结合与催化的空间相互作用而以某种方式被破坏。成对序列同一性通常不显著，并且几乎一半的酶和非酶对在功能上没有任何相似性。还讨论了由同源亚基组成的异源寡聚酶，其中一条链催化无活性，以及包含古老酶结构域内部催化和非催化重复的酶多肽。
