Weizmann Institute of Science, Department of Biomolecular Sciences, Rehovot, Israel.
University of Haifa, Department of Computer Science, Haifa, Israel.
Elife. 2020 Dec 9;9:e64415. doi: 10.7554/eLife.64415.
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.
本文是为纪念 Michael G. Rossmann 而作。回溯到最后一个普遍共同祖先，P 环 NTP 酶和 Rossmann 结构域构成了最普遍和最多样化的酶家族。尽管它们在整体结构和磷酸结合基序上存在相似之处，但缺乏序列同一性和一些基本的结构差异，目前将它们划分为独立的分支。我们系统地搜索了这两个家族共有的结构和序列元件。我们检测到跨越两个家族的第一个 βαβ 模体的同源片段，包括磷酸结合环和β2 末端的保守天冬氨酸。后者在 P 环 NTP 酶中连接催化金属，而在 Rossmann 结构域中，它结合核苷酸的核糖部分。微管蛋白，一种 Rossmann GTP 酶，展示了 β2-天冬氨酸具有这两种功能的潜力。虽然不能完全排除趋同进化的可能性，但我们表明，这两个家族可能都起源于一个共同的 βαβ 片段，这个片段至今仍是这些酶家族的核心。
