On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment.
On the emergence of P-Loop NTPase and Rossmann enzymes from a Beta-Alpha-Beta ancestral fragment.
复制标题
从β-α-β祖先片段中出现P环NTR和Rossmann酶。
DOI：
10.7554/elife.64415
复制
发表时间：
2020-12-09
期刊：
影响因子：
7.7
通讯作者：
Tawfik DS
中科院分区：
文献类型：
--
作者：
Longo LM;Jabłońska J;Vyas P;Kanade M;Kolodny R;Ben-Tal N;Tawfik DS
这篇文章是为了纪念迈克尔·g·罗斯曼。追溯到最后一个普遍的共同祖先，p环NTPases和Rossmanns构成了最普遍和多样化的酶谱系。尽管它们的整体结构和磷酸盐结合基序相似，但缺乏序列同一性和一些基本的结构差异目前使它们成为独立的出现。我们系统地搜索了两个谱系共有的结构和序列元素。我们在两个谱系中发现了跨越第一个βαβ基序的同源片段，包括磷酸结合环和β2尖端的保守天冬氨酸。后者连接p环NTPases中的催化金属，而在Rossmanns中，它结合核苷酸的核糖部分。微管蛋白是一种罗斯曼GTPase，它显示了β2-Asp发挥这两种作用之一的潜力。虽然不能完全排除趋同的可能性，但我们表明，这两个谱系可能都来自一个共同的βαβ片段，该片段至今仍是这些酶家族的核心。
This article is dedicated to the memory of Michael G. Rossmann. Dating back to the last universal common ancestor, P-loop NTPases and Rossmanns comprise the most ubiquitous and diverse enzyme lineages. Despite similarities in their overall architecture and phosphate binding motif, a lack of sequence identity and some fundamental structural differences currently designates them as independent emergences. We systematically searched for structure and sequence elements shared by both lineages. We detected homologous segments that span the first βαβ motif of both lineages, including the phosphate binding loop and a conserved aspartate at the tip of β2. The latter ligates the catalytic metal in P-loop NTPases, while in Rossmanns it binds the nucleotide’s ribose moiety. Tubulin, a Rossmann GTPase, demonstrates the potential of the β2-Asp to take either one of these two roles. While convergence cannot be completely ruled out, we show that both lineages likely emerged from a common βαβ segment that comprises the core of these enzyme families to this very day.