Catazaro Jonathan, Caprez Adam, Guru Ashu, Swanson David, Powers Robert
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, 68588-0304.
Proteins. 2014 Oct;82(10):2597-608. doi: 10.1002/prot.24624. Epub 2014 Jun 20.
Families of distantly related proteins typically have very low sequence identity, which hinders evolutionary analysis and functional annotation. Slowly evolving features of proteins, such as an active site, are therefore valuable for annotating putative and distantly related proteins. To date, a complete evolutionary analysis of the functional relationship of an entire enzyme family based on active-site structural similarities has not yet been undertaken. Pyridoxal-5'-phosphate (PLP) dependent enzymes are primordial enzymes that diversified in the last universal ancestor. Using the comparison of protein active site structures (CPASS) software and database, we show that the active site structures of PLP-dependent enzymes can be used to infer evolutionary relationships based on functional similarity. The enzymes successfully clustered together based on substrate specificity, function, and three-dimensional-fold. This study demonstrates the value of using active site structures for functional evolutionary analysis and the effectiveness of CPASS.
亲缘关系较远的蛋白质家族通常具有非常低的序列同一性，这阻碍了进化分析和功能注释。因此，蛋白质的缓慢进化特征，如活性位点，对于注释推定的和远缘相关的蛋白质很有价值。迄今为止，尚未基于活性位点结构相似性对整个酶家族的功能关系进行完整的进化分析。磷酸吡哆醛（PLP）依赖性酶是在最后一个共同祖先中多样化的原始酶。使用蛋白质活性位点结构比较（CPASS）软件和数据库，我们表明PLP依赖性酶的活性位点结构可用于基于功能相似性推断进化关系。这些酶基于底物特异性、功能和三维折叠成功地聚集在一起。这项研究证明了使用活性位点结构进行功能进化分析的价值以及CPASS的有效性。
