Hypoxanthine‐guanine phosphoribosyltransferase is activated via positive cooperativity between guanine and IMP. Issue 8 (10th February 2022)

• Record Type: Journal Article
• Authors: Ueda, Shigeru; Hirata, Tatsuya; Sakasegawa, Shin‐ichi
• Is Part Of: FEBS letters. Volume 596:Issue 8(2022)
• Page Start: 1072
• Page End: 1080
• Publication Date: 2022-02-10
• Subjects: guanine activation -- hypoxanthine‐guanine phosphoribosyltransferase -- IMP‐pyrophosphorolysis -- positive cooperativity; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14306
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : As is the case with human hypoxanthine‐guanine phosphoribosyltransferase (HGPRT), we confirmed that the IMP pyrophosphorolysis reaction of HGPRT from the thermophilic bacterium Hungateiclostridium thermocellum is activated by guanine (Gua). The K m indicated that IMP and Gua acted in a noncompetitive manner. Our kinetic model suggests that the oligomer with an unoccupied site preferentially forms a chimeric oligomer with IMP and Gua.