8S3A
Crystal structure of Medicago truncatula glutamate dehydrogenase 2 in complex with 2,6-pyridinedicarboxylic acid and NAD
Summary for 8S3A
| Entry DOI | 10.2210/pdb8s3a/pdb |
| Descriptor | Glutamate dehydrogenase, (4S)-2-METHYL-2,4-PENTANEDIOL, 1,2-ETHANEDIOL, ... (10 entities in total) |
| Functional Keywords | complex with inhibitor, glutamate dehydrogenase, oxidoreductase |
| Biological source | Medicago truncatula (barrel medic) |
| Total number of polymer chains | 6 |
| Total formula weight | 275796.99 |
| Authors | |
| Primary citation | Grzechowiak, M.,Sliwiak, J.,Link, A.,Ruszkowski, M. Legume-type glutamate dehydrogenase: Structure, activity, and inhibition studies. Int.J.Biol.Macromol., 278:134648-134648, 2024 Cited by PubMed Abstract: Glutamate dehydrogenases (GDHs) are key enzymes at the crossroads of N and C metabolism in plants. Legumes, whose N metabolism is particularly intricate, possess a unique type of GDH. This study presents an analysis of a legume-type GDH (isoform 2) from Medicago truncatula (MtGDH2). We measured MtGDH2 activity in both the Glu → 2-oxoglutarate (2OG) and 2OG → Glu reaction directions and obtained kinetic parameters for Glu, 2OG, NAD, and NADH. Inhibition assays revealed that compounds possessing di- or tricarboxylates act as inhibitors of plant GDHs. Interestingly, 2,6-pyridinedicarboxylate (PYR) weakly inhibits MtGDH2 compared to Arabidopsis thaliana homologs. Furthermore, we explored tetrazole derivatives to discover 3-(1H-tetrazol-5-yl)benzoic acid (TBA) as an MtGDH2 inhibitor. The kinetic experiments are supported by six crystal structures, solved as: (i) unliganded enzyme, (ii) trapping the reaction intermediate 2-amino-2-hydroxyglutarate and NAD, and also complexed with NAD and inhibitors such as (iii) citrate, (iv) PYR, (v) isophthalate, and (vi) TBA. The complex with TBA revealed a new mode of action that, in contrast to other inhibitors, prevents domain closure. This discovery points to TBA as a starting point for the development of novel GDH inhibitors to study the functions of GDH in plants and potentially boost biomass production. PubMed: 39142482DOI: 10.1016/j.ijbiomac.2024.134648 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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