Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801 A, Derio, Spain.
Centro Nacional de Biotecnología, CNB-CSIC, Darwin 3, Madrid, Spain.
Commun Biol. 2021 Jun 3;4(1):684. doi: 10.1038/s42003-021-02222-x.
Glutamate dehydrogenases (GDHs) are widespread metabolic enzymes that play key roles in nitrogen homeostasis. Large glutamate dehydrogenases composed of 180 kDa subunits (L-GDHs) contain long N- and C-terminal segments flanking the catalytic core. Despite the relevance of L-GDHs in bacterial physiology, the lack of structural data for these enzymes has limited the progress of functional studies. Here we show that the mycobacterial L-GDH (mL-GDH) adopts a quaternary structure that is radically different from that of related low molecular weight enzymes. Intersubunit contacts in mL-GDH involve a C-terminal domain that we propose as a new fold and a flexible N-terminal segment comprising ACT-like and PAS-type domains that could act as metabolic sensors for allosteric regulation. These findings uncover unique aspects of the structure-function relationship in the subfamily of L-GDHs.
谷氨酸脱氢酶（GDHs）是广泛存在的代谢酶，在氮平衡中起着关键作用。由 180kDa 亚基组成的大型谷氨酸脱氢酶（L-GDHs）含有侧翼催化核心的长 N-和 C-末端片段。尽管 L-GDHs 在细菌生理学中具有重要意义，但这些酶缺乏结构数据限制了功能研究的进展。在这里，我们表明分枝杆菌的 L-GDH（mL-GDH）采用了一种与相关低分子量酶截然不同的四级结构。mL-GDH 中的亚基间接触涉及一个 C-末端结构域，我们将其提议为一个新的折叠，以及一个包含 ACT 样和 PAS 型结构域的灵活 N-末端片段，该片段可能作为变构调节的代谢传感器。这些发现揭示了 L-GDH 亚家族结构-功能关系的独特方面。
