+検索条件
-Structure paper
| タイトル | Tertiary and quaternary structure remodeling by occupancy of the substrate binding pocket in a large glutamate dehydrogenase. |
|---|---|
| ジャーナル・号・ページ | Protein Sci, Vol. 35, Issue 4, Page e70544, Year 2026 |
| 掲載日 | 2026年3月25日 |
著者 | Melisa Lázaro / Nicolás Chamorro / Jorge P López-Alonso / Diego Charro / Rodolfo M Rasia / Gonzalo Jiménez-Osés / Mikel Valle / María-Natalia Lisa / ![]() |
| PubMed 要旨 | Glutamate dehydrogenases (GDHs) catalyze the oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P) as a cofactor. The large type of GDHs (L-GDHs) displays a dynamic homotetrameric ...Glutamate dehydrogenases (GDHs) catalyze the oxidative deamination of L-glutamate to 2-oxoglutarate using NAD(P) as a cofactor. The large type of GDHs (L-GDHs) displays a dynamic homotetrameric architecture that alternates between open and closed states. However, the catalytic mechanism and the functional relevance of the large conformational changes in L-GDHs remain poorly understood. Here, we use cryo-EM to investigate the structure and the conformational landscape of the mycobacterial L-GDH composed of 180 kDa subunits (mL-GDH) when incubated with L-glutamate and NAD. Classification of the heterogeneous population of tetramers reveals opening-closing motions and sorting of individual subunits resolves the occupancy of the cofactor and substrate binding pockets. Cryo-EM maps show that ligand binding to the glutamate binding pocket is accompanied by structural changes in a region approximately two nanometers away from the active site, leading to the formation of a previously undetected interaction between the catalytic domains of neighboring subunits in mL-GDH closed tetrameric states. Our findings indicate that the occupancy of the substrate binding site of mL-GDH is linked to a remodeling of both the tertiary and quaternary structure of the enzyme. |
リンク | Protein Sci / PubMed:41877587 |
| 手法 | EM (単粒子) |
| 解像度 | 2.63 - 4.1 Å |
| 構造データ | EMDB-52419: CryoEM map of the large glutamate dehydrogenase composed of 180 kDa subunits from Mycobacterium smegmatis obtained in the presence of NAD+ and L-glutamate. Open Tetramer EMDB-52420, PDB-9huy: EMDB-52421, PDB-9huz: EMDB-52422, PDB-9hv0: EMDB-52423, PDB-9hv4: EMDB-52424, PDB-9hv5: ![]() EMDB-52425: CryoEM map of the large glutamate dehydrogenase composed of 180 kDa subunits from Mycobacterium smegmatis obtained in the presence of NAD+ and L-glutamate. cofactor/ligand-monomer in Open tetramer. ![]() EMDB-52426: CryoEM map of the large glutamate dehydrogenase composed of 180 kDa subunits from Mycobacterium smegmatis obtained in the presence of NAD+ and L-glutamate. cofactor/ligand-monomer in Closed1 tetramer. ![]() EMDB-52427: CryoEM map of the large glutamate dehydrogenase composed of 180 kDa subunits from Mycobacterium smegmatis obtained in the presence of NAD+ and L-glutamate. cofactor/ligand-monomer in Closed2 tetramer. EMDB-52428, PDB-9hv6: ![]() EMDB-52429: CryoEM map of the large glutamate dehydrogenase composed of 180 kDa subunits from Mycobacterium smegmatis obtained in the presence of NAD+ and L-glutamate. Closed2 tetramer with cofactor/ligand-monomer. |
| 化合物 | ![]() ChemComp-NAD: ![]() ChemComp-GLU: |
| 由来 |
|
キーワード | OXIDOREDUCTASE / Large glutamate dehydrogenase / Tetramer |
ムービー
コントローラー
構造ビューア
万見文献について



著者

リンク



















mycolicibacterium smegmatis (バクテリア)
キーワード