scholarly journals Molecular insights into the inhibition of glutamate dehydrogenase ( GDH ) by the dicarboxylic acid metabolites

2021 ◽  
Author(s):  
Barsa Kanchan Jyotshna Godsora ◽  
Prem Prakash ◽  
Narayan S. Punekar ◽  
Prasenjit Bhaumik
Keyword(s):  
Dicarboxylic Acid ◽  
Glutamate Dehydrogenase ◽  
Acid Metabolites

scholarly journals Molecular insights into the inhibition of glutamate dehydrogenase (GDH) by the dicarboxylic acid metabolites

2021 ◽  
Author(s):  
Barsa Kanchan Jyotshna Godsora ◽  
Prem Prakash ◽  
Narayan S. Punekar ◽  
Prasenjit Bhaumik
Keyword(s):  
Dicarboxylic Acid ◽  
Glutamate Dehydrogenase ◽  
Active Site ◽  
Binding Pocket ◽  
Metabolic Enzyme ◽  
Carbon And Nitrogen ◽  
Carboxylate Groups ◽  
Lysine Residues ◽  
Acid Metabolites ◽  
Living Organisms

Glutamate dehydrogenase (GDH) is a salient metabolic enzyme which catalyzes the NAD+- or NADP+-dependent reversible conversion of α-ketoglutarate (AKG) to L-glutamate; and thereby connects the carbon and nitrogen metabolism cycles in all living organisms. The function of GDH is extensively regulated by both metabolites (citrate, succinate, etc.) and non-metabolites (ATP, NADH, etc.) but sufficient molecular evidences are lacking to rationalize the inhibitory effects by the metabolites. We have expressed and purified NADP+-dependent Aspergillus terreus GDH (AtGDH) in recombinant form. Succinate, malonate, maleate, fumarate and tartrate independently inhibit the activity of AtGDH to different extents. The crystal structures of AtGDH complexed with the dicarboxylic acid metabolites and the coenzyme NADPH have been determined. Although AtGDH structures are not complexed with substrate; surprisingly, they acquire super closed conformation like previously reported for substrate and coenzyme bound catalytically competent Aspergillus niger GDH (AnGDH). These dicarboxylic acid metabolites partially occupy the same binding pocket as substrate; but interact with varying polar interactions and the coenzyme NADPH binds to the Domain-II of AtGDH. The low inhibition potential of tartrate as compared to other dicarboxylic acid metabolites is due to its weaker interactions of carboxylate groups with AtGDH. Our results suggest that the length of carbon skeleton and positioning of the carboxylate groups of inhibitors between two conserved lysine residues at the GDH active site might be the determinants of their inhibitory potency. Molecular details on the dicarboxylic acid metabolites bound AtGDH active site architecture presented here would be applicable to GDHs in general.

Properties of glutamate dehydrogenase from developing maize endosperm

1990 ◽  
Vol 80 (2) ◽  
pp. 238-242 ◽  
Author(s):  
Vesna Hadzi-TaskovicSukalovic
Keyword(s):  
Glutamate Dehydrogenase ◽  
Maize Endosperm

Bacterial Mercapturic Acid Metabolites

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
PJ Proteau
Keyword(s):  
Mercapturic Acid ◽  
Acid Metabolites

Efficient One-pot HATU Mediated Coupling of Dicarboxylic Acid and Amines for the Synthesis of Diamide at Ambient Temperature

2017 ◽  
Vol 14 (10) ◽  
Author(s):  
Vimal Bhatt ◽  
S. D. Samant ◽  
Suhas Pednekar
Keyword(s):  
Ambient Temperature ◽  
Dicarboxylic Acid ◽  
One Pot

SYNTHESIS, CHARACTERIZATION, DNA BINDING, AND ANTICANCER ABILITY OF A Co(II) COMPLEX CONSTRUCTED BY 2-PROPYL-1H-IMIDAZOLE-4,5-DICARBOXYLIC ACID

2020 ◽  
Vol 61 (12) ◽  
pp. 1938-1944
Author(s):  
S. Wu ◽  
S. Wang ◽  
M. Zhu ◽  
E. Gao
Keyword(s):  
Dna Binding ◽  
Dicarboxylic Acid
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