Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions
Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions
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DOI：
10.1021/ja0466457
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发表时间：
2004-12-22
影响因子：
15
通讯作者：
Kanehisa, M
中科院分区：
文献类型：
--
作者：
Kotera, M;Okuno, Y;Kanehisa, M
EC（酶委员会）编号代表酶促反应的层次分类，但它们也通常在完整基因组分析中用作酶或酶基因的标识符。 EC 数的这种二元性使得将酶基因的基因组库与代谢途径的化学库联系起来成为可能，该过程称为代谢重建。不幸的是，已知有许多反应存在于各种途径中，但它们永远不会获得 EC 编号，因为 EC 编号分配需要发表有关酶的完整表征的文章。在这里，我们报告了一种计算机化方法，可以自动将 EC 编号分配给子子类，即，在给定底物和产品对的情况下，无需用于底物特异性的第四个序列号。该方法基于一种新的酶促反应分类方案，称为 RC（反应分类）数。当前 EC 数数据集中的每个反应首先被分解为反应物对。然后对每一对进行结构比对，以识别反应中心、匹配区域和差异区域。 RC数代表这三个区域中原子类型的转换模式。我们通过折刀交叉验证测试检查了计算分配的 RC 编号和手动分配的 EC 编号之间的对应关系，发现 EC 子类的分配准确度约为 90%。此外，我们检查了与 KEGG 直系同源簇 (OC) 所代表的基因组信息的相关性，并确认 RC 数不仅与基本反应机制相关，而且与蛋白质家族相关。
The EC (Enzyme Commission) numbers represent a hierarchical classification of enzymatic reactions, but they are also commonly utilized as identifiers of enzymes or enzyme genes in the analysis of complete genomes. This duality of the EC numbers makes it possible to link the genomic repertoire of enzyme genes to the chemical repertoire of metabolic pathways, the process called metabolic reconstruction. Unfortunately, there are numerous reactions known to be present in various pathways, but they will never get EC numbers because the EC number assignment requires published articles on full characterization of enzymes. Here we report a computerized method to automatically assign the EC numbers up to the sub-subclasses, i.e., without the fourth serial number for substrate specificity, given pairs of substrates and products. The method is based on a new classification scheme of enzymatic reactions, named the RC (reaction classification) number. Each reaction in the current dataset of the EC numbers is first decomposed into reactant pairs. Each pair is then structurally aligned to identify the reaction center, the matched region, and the difference region. The RC number represents the conversion patterns of atom types in these three regions. We examined the correspondence between computationally assigned RC numbers and manually assigned EC numbers by the jackknife cross-validation test and found that the EC sub-subclasses could be assigned with the accuracy of about 90%. Furthermore, we examined the correlation with genomic information as represented by the KEGG ortholog clusters (OC) and confirmed that the RC numbers are correlated not only with elementary reaction mechanisms but also with protein families.