The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase
The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase
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DOI：
10.1093/emboj/21.9.2068
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发表时间：
2002-05-01
期刊：
影响因子：
11.4
通讯作者：
Warren, MJ
中科院分区：
文献类型：
--
作者：
Schubert, HL;Raux, E;Warren, MJ
Sirohaem是一种四吡咯衍生的辅基，作为亚硫酸盐和亚硝酸盐还原酶系统的一部分，它是所有生命系统中硫和氮的基本同化所必需的。在sirohaem的生物合成中的最后两个步骤涉及前咕啉-2的β-NAD（+）-依赖性脱氢以产生sirohydrochlorin，然后是亚铁螯合以产生sirohaem。在酿酒酵母中，Met 8 p是进行这两种反应的双功能酶。在这里，我们报告的2.2埃分辨率的晶体结构的Met 8 p，它采用了一种新的折叠，不承担类似于以前确定的结构的钴或铁螯合酶。突变蛋白的分析表明，这两种催化活性共享一个单一的活性位点，Asp 141在脱氢酶和螯合酶过程中起着至关重要的作用。
Sirohaem is a tetrapyrrole-derived prosthetic group that is required for the essential assimilation of sulfur and nitrogen into all living systems as part of the sulfite and nitrite reductase systems. The final two steps in the biosynthesis of sirohaem involve a beta-NAD(+)-dependent dehydrogenation of precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield sirohaem. In Saccharomyces cerevisiae, Met8p is a bifunctional enzyme that carries out both of these reactions. Here, we report the 2.2 Angstrom resolution crystal structure of Met8p, which adopts a novel fold that bears no resemblance to the previously determined structures of cobalt- or ferro-chelatases. Analysis of mutant proteins suggests that both catalytic activities share a single active site, and that Asp141 plays an essential role in both dehydrogenase and chelatase processes.