Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States.
J Mol Biol. 2023 Jun 1;435(11):167965. doi: 10.1016/j.jmb.2023.167965. Epub 2023 Jun 16.
Nucleoside-triphosphate hydrolases (NTPases) are a diverse, but essential group of enzymes found in all living organisms. NTPases that have a G-X-X-X-X-G-K-[S/T] consensus sequence (where X is any amino acid), known as the Walker A or P-loop motif, constitute a superfamily of P-loop NTPases. A subset of ATPases within this superfamily contains a modified Walker A motif, X-K-G-G-X-G-K-[S/T], wherein the first invariant lysine residue is essential to stimulate nucleotide hydrolysis. Although the proteins in this subset have vastly differing functions, ranging from electron transport during nitrogen fixation to targeting of integral membrane proteins to their correct membranes, they have evolved from a shared ancestor and have thus retained common structural features that affect their functions. These commonalities have only been disparately characterized in the context of their individual proteins systems, but have not been generally annotated as features that unite the members of this family. In this review, we report an analysis based on the sequences, structures, and functions of several members in this family that highlight their remarkable similarities. A principal feature of these proteins is their dependence on homodimerization. Since their functionalities are heavily influenced by changes that happen in conserved elements at the dimer interface, we refer to the members of this subclass as intradimeric Walker A ATPases.
核苷三磷酸水解酶（NTPases）是一种广泛存在于所有生物体内的必需酶类，具有高度多样性。具有 G-X-X-X-X-G-K-[S/T] 共识序列（其中 X 是任何氨基酸）的 NTPases，称为 Walker A 或 P 环基序，构成了 P 环 NTPase 的超家族。该超家族中的一部分 ATPases 包含一个修饰的 Walker A 基序，X-K-G-G-X-G-K-[S/T]，其中第一个不变的赖氨酸残基对于刺激核苷酸水解至关重要。尽管这个亚类中的蛋白质具有截然不同的功能，从氮固定过程中的电子传递到靶向整合膜蛋白到它们正确的膜，它们是从一个共同的祖先进化而来的，因此保留了影响其功能的共同结构特征。这些共性在它们各自的蛋白质系统中已经得到了不同程度的描述，但并没有被普遍注释为将这个家族成员统一起来的特征。在这篇综述中，我们报告了基于该家族几个成员的序列、结构和功能的分析，强调了它们的显著相似性。这些蛋白质的一个主要特征是它们依赖于同源二聚化。由于它们的功能受到二聚体界面上保守元素变化的严重影响，我们将这个亚类的成员称为二聚体 Walker A ATPase。
