Hypoxanthine‐guanine phosphoribosyltransferase is activated via positive cooperativity between guanine and IMP

Abstract

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme in the purine salvage pathway. Here, the reverse reaction of HGPRT from the thermophilic bacterium Hungateiclostridium thermocellum was studied in the presence of IMP and pyrophosphate. As for the human enzyme, the bacterial HGPRT was activated by guanine. Furthermore, guanine was found to operate as both an activator and an inhibitor. Intriguingly, within the concentration range of guanine where it functions as the activator, the K m value for IMP was not influenced by guanine. Consequently, guanine was found to noncompetitively activate the reverse reaction toward IMP. Here, we propose a reaction scheme that explains the activation mechanism in which the enzyme forms a chimeric oligomer bound to both IMP and guanine.

RNA sequencing and proteomic profiling reveal alterations by MPTP in chronic stomach mucosal injury in tree shrew Chinese (Tupaia belangeri chinensis)

“…3 B–D). Hypoxanthine–guanine phosphoribosyltransferase (HGPRT, also known as HPRT1) is a key enzyme in the purine salvage pathway 12 . DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle 13 .…”

Susceptibility genes of hyperuricemia and gout

“…1 , HPRT is the most important enzyme in the purine salvage pathway, which catalyzes the synthesis of hypoxanthine into hypoxanthine nucleotides and the conversion of guanine into guanine nucleotides. Its activity is regulated by the synergistic effect of guanine and IMP [ 28 ]. HPRT gene mutation can cause HPRT enzyme activity defect, then it will lead to the surplus of its substrates hypoxanthine and guanine, and these surplus purines will be converted into UA under the action of xanthine oxidase (XO) (Fig.…”