Galperin M Y, Walker D R, Koonin E V
National Center for Biotechnology Information (NCBI), National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA.
Genome Res. 1998 Aug;8(8):779-90. doi: 10.1101/gr.8.8.779.
It is known that the same reaction may be catalyzed by structurally unrelated enzymes. We performed a systematic search for such analogous (as opposed to homologous) enzymes by evaluating sequence conservation among enzymes with the same enzyme classification (EC) number using sensitive, iterative sequence database search methods. Enzymes without detectable sequence similarity to each other were found for 105 EC numbers (a total of 243 distinct proteins). In 34 cases, independent evolutionary origin of the suspected analogous enzymes was corroborated by showing that they possess different structural folds. Analogous enzymes were found in each class of enzymes, but their overall distribution on the map of biochemical pathways is patchy, suggesting multiple events of gene transfer and selective loss in evolution, rather than acquisition of entire pathways catalyzed by a set of unrelated enzymes. Recruitment of enzymes that catalyze a similar but distinct reaction seems to be a major scenario for the evolution of analogous enzymes, which should be taken into account for functional annotation of genomes. For many analogous enzymes, the bacterial form of the enzyme is different from the eukaryotic one; such enzymes may be promising targets for the development of new antibacterial drugs.
众所周知，相同的反应可能由结构不相关的酶催化。我们通过使用灵敏的迭代序列数据库搜索方法，评估具有相同酶分类（EC）编号的酶之间的序列保守性，对这类类似（而非同源）酶进行了系统搜索。对于105个EC编号（总共243种不同的蛋白质），发现了彼此之间没有可检测到的序列相似性的酶。在34个案例中，通过表明它们具有不同的结构折叠，证实了疑似类似酶的独立进化起源。在每一类酶中都发现了类似酶，但它们在生化途径图谱上的总体分布是不连续的，这表明在进化过程中发生了多次基因转移和选择性丢失事件，而不是获得了一组不相关酶催化的整个途径。催化相似但不同反应的酶的招募似乎是类似酶进化的主要情况，这在基因组功能注释中应予以考虑。对于许多类似酶来说，该酶的细菌形式与真核形式不同；这类酶可能是开发新型抗菌药物的有前景的靶点。
