Pils Birgit, Schultz Jörg
Department of Bioinformatics, Würzburg University, Biozentrum, Am Hubland, 97074 Würzburg, Germany.
J Mol Biol. 2004 Jul 9;340(3):399-404. doi: 10.1016/j.jmb.2004.04.063.
Although the catalytic center of an enzyme is usually highly conserved, there have been a few reports of proteins with substitutions at essential catalytic positions, which convert the enzyme into a catalytically inactive form. Here, we report a large-scale analysis of substitutions at enzymes' catalytic sites in order to gain insight into the function and evolution of inactive enzyme-homologues. Our analysis revealed that inactive enzyme-homologues are not an exception only found in single enzyme families, but that they are represented in a large variety of enzyme families and conserved among metazoan species. Even though they have lost their catalytic activity, they have adopted new functions and are now mainly involved in regulatory processes, as shown by several case studies. This modification of existing modules is an efficient mechanism to evolve new functions. The invention of inactive enzyme-homologues in metazoa has thereby led to an enhancement of complexity of regulatory networks.
尽管酶的催化中心通常高度保守，但已有一些关于蛋白质在关键催化位点发生取代的报道，这些取代会将酶转化为无催化活性的形式。在此，我们报告了对酶催化位点取代的大规模分析，以便深入了解无活性酶同源物的功能和进化。我们的分析表明，无活性酶同源物并非仅在单个酶家族中出现的例外情况，而是存在于各种各样的酶家族中，并在后生动物物种中保守。尽管它们失去了催化活性，但已获得了新功能，目前主要参与调节过程，几个案例研究表明了这一点。对现有模块的这种修饰是进化出新功能的有效机制。后生动物中无活性酶同源物的出现从而导致了调节网络复杂性的增强。
