EC Number   |
General Information |
Reference |
|---|
   1.4.1.3 | drug target |
the ADP-ribosylation of glutamate dehydrogenase is catalyzed by Sirt4, and downregulates the TCA cycle. In the ternary complex model of Sirt4-NAD+-GDH, the acetylated lysine 171 of GDH is located close to NAD+. This suggests a possible mechanism underlying the ADP-ribosylation at cysteine 172, which may occur through a transient intermediate with ADP-ribosylation at the acetylated lysine 171 |
762936 |
| 1.4.1.3 | evolution |
GDH is a widely distributed enzyme among all domains of life. Mammalian GDH is regulated allosterically by multiple metabolites, in which the antenna helix plays a key role to transmit the allosteric signals. In contrast, bacterial GDH is believed not to be regulated allosterically because it lacks the antenna helix |
759432 |
| 1.4.1.3 | evolution |
hGDH2 emerged recently via retroposition during primate evolution, being only present in humans and some closely related great apes. Functional evolution of hGDH isoenzymes, overview. Reflecting the very recent emergence of hGDH2 from hGDH1, the two human proteins show very high amino acid sequence homology (about 97%), differing in only 15 of 505 amino acids in their mature forms. Despite this similarity, hGDH2 has unique enzymatic and regulatory properties. These include GTP resistance and low basal activity amenable to activation by ADP and/or L-leucine, lower optimal pH and relative sensitivity to thermal inactivation. These properties are to a large extent associated with only two of the 15 amino acid substitutions that occurred in the course of hGDH2 evolution. In particular, the Gly456 to Ala substitution confers GTP resistance, whereas the Arg443 to Ser change is associated with lower basal activity, though still permitting activation by ADP |
763376 |
| 1.4.1.3 | evolution |
reflecting the very recent emergence of hGDH2 from hGDH1, the two human proteins show very high amino acid sequence homology (about 97%), differing in only 15 of 505 amino acids in their mature forms. Despite this similarity, hGDH2 has unique enzymatic and regulatory properties |
763376 |
| 1.4.1.3 | evolution |
while GDH in most mammals is encoded by a single GLUD1 gene, humans and other primates have acquired a GLUD2 gene with distinct tissue expression profile |
725866 |
| 1.4.1.3 | evolution |
while most mammals possess a single GDH1 protein (hGDH1 in the human) that is highly expressed in the liver, humans and other primates have acquired, via duplication, an hGDH2 isoenzyme with distinct functional properties and tissue expression profile. hGDH2 underwent rapid evolutionary adaptation, acquiring unique properties that enable enhanced enzyme function under conditions inhibitory to its ancestor hGDH1. These are thought to provide a biological advantage to humans with hGDH2 evolution occurring concomitantly with human brain development |
762783 |
| 1.4.1.3 | evolution |
while most mammals possess a single GDH1 protein (hGDH1 in the human) that is highly expressed in the liver, humans and other primates have acquired, via duplication, an hGDH2 isoenzyme with distinct functional properties and tissue expression profile. hGDH2 underwent rapid evolutionary adaptation, acquiring unique properties that enable enhanced enzyme function under conditions inhibitory to its ancestor hGDH1. These are thought to provide a biological advantage to humans with hGDH2 evolution occurring concomitantly with human brain development. A major evolutionary adaptation of hGDH2 is the ability of the enzyme to downregulate its activity in the absence of allosteric effectors |
762783 |
| 1.4.1.3 | malfunction |
deregulation of hGDH1/2 is implicated in the pathogenesis of several human disorders |
762783 |
| 1.4.1.3 | malfunction |
deregulation of hGDH1/2 is implicated in the pathogenesis of several human disorders. Glioma cells with the R132H IDH1 mutation show selective inhibition of GLUD2 expression markedly slows cell growth. xpression of GLUD2 (but not GLUD1) promotes tumor expansion, suggesting that R132H IDH1 glioma cells proliferate by utilizing enhanced glutamate flux through the GLUD2 pathway |
762783 |
| 1.4.1.3 | malfunction |
growth analysis of the aprth knockout strain (Tt27DELTAAPRTh) and aprth-overexpressing strain (Tt27NStHisAPRTh) of Thermus thermophilus in minimal medium. The Tt27DELTAAPRTh strain exhibits delayed growth and requires approximately 36 h to reach the early stationary phase, whereas the wild-type strain reaches this phase after 21 h of cultivation. The overexpressing Tt27NStHisAPRTh strain exhibits better growth than even the wild-type strain |
759432 |
