8HIQ
cryoEM structure of glutamate dehydrogenase from Thermococcus profundus in complex with NADP
Summary for 8HIQ
| Entry DOI | 10.2210/pdb8hiq/pdb |
| Related | 8HHO |
| EMDB information | 34826 |
| Descriptor | Glutamate dehydrogenase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (2 entities in total) |
| Functional Keywords | complex, coenzyme, nadp, oxidoreductase |
| Biological source | Thermococcus profundus |
| Total number of polymer chains | 1 |
| Total formula weight | 47501.88 |
| Authors | Wakabayashi, T.,Oide, M.,Kato, T.,Nakasako, M. (deposition date: 2022-11-21, release date: 2023-02-08, Last modification date: 2023-12-20) |
| Primary citation | Wakabayashi, T.,Oide, M.,Kato, T.,Nakasako, M. Coenzyme-binding pathway on glutamate dehydrogenase suggested from multiple-binding sites visualized by cryo-electron microscopy. Febs J., 290:5514-5535, 2023 Cited by PubMed Abstract: The structure of hexameric glutamate dehydrogenase (GDH) in the presence of the coenzyme nicotinamide adenine dinucleotide phosphate (NADP) was visualized using cryogenic transmission electron microscopy to investigate the ligand-binding pathways to the active site of the enzyme. Each subunit of GDH comprises one hexamer-forming core domain and one nucleotide-binding domain (NAD domain), which spontaneously opens and closes the active-site cleft situated between the two domains. In the presence of NADP, the potential map of GDH hexamer, assuming D3 symmetry, was determined at a resolution of 2.4 Å, but the NAD domain was blurred due to the conformational variety. After focused classification with respect to the NAD domain, the potential maps interpreted as NADP molecules appeared at five different sites in the active-site cleft. The subunits associated with NADP molecules were close to one of the four metastable conformations in the unliganded state. Three of the five binding sites suggested a pathway of NADP molecules to approach the active-site cleft for initiating the enzymatic reaction. The other two binding modes may rarely appear in the presence of glutamate, as demonstrated by the reaction kinetics. Based on the visualized structures and the results from the enzymatic kinetics, we discussed the binding modes of NADP to GDH in the absence and presence of glutamate. PubMed: 37682540DOI: 10.1111/febs.16951 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
Download full validation report
