| First Author | Ma T | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 41882 | PubMed ID | 28139779 |
| Mgi Jnum | J:330410 | Mgi Id | MGI:7378661 |
| Doi | 10.1038/srep41882 | Citation | Ma T, et al. (2017) The beta and gamma subunits play distinct functional roles in the alpha2betagamma heterotetramer of human NAD-dependent isocitrate dehydrogenase. Sci Rep 7:41882 |
| abstractText | Human NAD-dependent isocitrate dehydrogenase existing as the alpha2betagamma heterotetramer, catalyzes the decarboxylation of isocitrate into alpha-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory beta and gamma subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing alphabeta and alphagamma heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that alphabeta and alphagamma alone have considerable basal activity but the full activity of alpha2betagamma requires the assembly and cooperative function of both heterodimers. alpha2betagamma and alphagamma can be activated by citrate or/and ADP, whereas alphabeta cannot. The binding of citrate or/and ADP decreases the S0.5,isocitrate and thus enhances the catalytic efficiencies of the enzymes, and the two activators can act independently or synergistically. Moreover, ATP can activate alpha2betagamma and alphagamma at low concentration and inhibit the enzymes at high concentration, but has only inhibitory effect on alphabeta. Furthermore, the allosteric activation of alpha2betagamma is through the gamma subunit not the beta subunit. These results demonstrate that the gamma subunit plays regulatory role to activate the holoenzyme, and the beta subunit the structural role to facilitate the assembly of the holoenzyme. |
