8Z2F

Cryo-EM structure of apo Aspergillus terreus glutamate dehydrogenase (AtGDH) in the partially closed conformation (form 1)

8Z2F の概要

• エントリーDOI: 10.2210/pdb8z2f/pdb
• EMDBエントリー: 39744
• 分子名称: Glutamate dehydrogenase (1 entity in total)
• 機能のキーワード: glutamate dehydrogenase, allostery, cooperativity, aspergillus, cryo-em, domain dynamics, oxidoreductase
• 由来する生物種: Aspergillus terreus
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 295484.63

構造登録者

Godsora, B.K.J.,Das, P.,Bhaumik, P. (登録日: 2024-04-12, 公開日: 2025-03-05)

主引用文献

Godsora, B.K.J.,Das, P.,Mishra, P.K.,Sairaman, A.,Kaledhonkar, S.,Punekar, N.S.,Bhaumik, P.
Conformational flexibility associated with remote residues regulates the kinetic properties of glutamate dehydrogenase.
Protein Sci., 34:e70038-e70038, 2025

PubMed Abstract: Glutamate dehydrogenase (GDH) is a pivotal metabolic enzyme in all living organisms, and some of the GDHs exhibit substrate-dependent homotropic cooperativity. However, the mode of allosteric communication during the homotropic effect in GDHs remains poorly understood. In this study, we examined two homologous GDHs, Aspergillus niger GDH (AnGDH) and Aspergillus terreus GDH (AtGDH), with differing substrate utilization kinetics to uncover the factors driving their distinct behavior. We report the crystal structures and first-ever cryo-EM structures of apo- AtGDH and AnGDH that captured arrays of conformational ensembles. A wider mouth opening (~ 21 Å) is observed for the cooperative AnGDH as compared to the non-cooperative AtGDH (~17 Å) in their apo states. A network of interactions related to the substitutions in Domain II influence structural flexibility in these GDHs. Remarkably, we have identified a distant substitution (R246 to S) in Domain II, as a part of this network, which can impact the mouth opening and converts non-cooperative AtGDH into a cooperative enzyme. Our study demonstrates that remote residues can influence structural and kinetic properties in homologous GDHs.

PubMed: 39981924
DOI: 10.1002/pro.70038

実験手法

ELECTRON MICROSCOPY (3.65 Å)