Otto Thomas D, Guimarães Ana Carolina R, Degrave Wim M, de Miranda Antonio B
Laboratory for Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil.
BMC Bioinformatics. 2008 Dec 17;9:544. doi: 10.1186/1471-2105-9-544.
Enzymes are responsible for the catalysis of the biochemical reactions in metabolic pathways. Analogous enzymes are able to catalyze the same reactions, but they present no significant sequence similarity at the primary level, and possibly different tertiary structures as well. They are thought to have arisen as the result of independent evolutionary events. A detailed study of analogous enzymes may reveal new catalytic mechanisms, add information about the origin and evolution of biochemical pathways and disclose potential targets for drug development.
In this work, we have constructed and implemented a new approach, AnEnPi (the Analogous Enzyme Pipeline), using a combination of bioinformatics tools like BLAST, HMMer, and in-house scripts, to assist in the identification, annotation, comparison and study of analogous and homologous enzymes. The algorithm for the detection of analogy is based i) on the construction of groups of homologous enzymes and ii) on the identification of cases where a given enzymatic activity is performed by two or more proteins without significant similarity between their primary structures. We applied this approach to a dataset obtained from KEGG Comprising all annotated enzymes, which resulted in the identification of 986 EC classes where putative analogy was detected (40.5% of all EC classes). AnEnPi is of considerable value in the construction of initial datasets that can be further curated, particularly in gene and genome annotation, in studies involving molecular evolution and metabolism and in the identification of new potential drug targets.
AnEnPi is an efficient tool for detection and annotation of analogous enzymes and other enzymes in whole genomes. It is available for academic use at: http://bioinfo.pdtis.fiocruz.br/AnEnPi/
酶负责催化代谢途径中的生化反应。类似酶能够催化相同的反应，但它们在一级结构上没有显著的序列相似性，三级结构可能也不同。它们被认为是独立进化事件的结果。对类似酶的详细研究可能会揭示新的催化机制，增加有关生化途径起源和进化的信息，并揭示药物开发的潜在靶点。
在这项工作中，我们构建并实施了一种新方法AnEnPi（类似酶管道），它结合了BLAST、HMMer等生物信息学工具和内部脚本，以协助识别、注释、比较和研究类似酶和同源酶。类似性检测算法基于：i）构建同源酶组；ii）识别由两种或更多种蛋白质执行给定酶活性且其一级结构之间无显著相似性的情况。我们将此方法应用于从KEGG获得的包含所有注释酶的数据集，结果识别出986个检测到假定类似性的酶委员会（EC）类别（占所有EC类别的40.5%）。AnEnPi在构建可进一步整理的初始数据集方面具有重要价值，特别是在基因和基因组注释、涉及分子进化和代谢的研究以及识别新的潜在药物靶点方面。
AnEnPi是用于检测和注释全基因组中类似酶及其他酶的有效工具。可在以下网址供学术使用：http://bioinfo.pdtis.fiocruz.br/AnEnPi/
