Structure, cooperativity and inhibition of the inosine 5'-monophosphate-specific phosphatase from Saccharomyces cerevisiae.

Autor: Byun S; Department of Agricultural Biotechnology, Seoul National University, Korea., Park C; Department of Agricultural Biotechnology, Seoul National University, Korea., Suh JY; Department of Agricultural Biotechnology, Seoul National University, Korea.; Research Institute of Agriculture and Life Sciences, Seoul National University, Korea., Witte CP; Department of Molecular Nutrition and Biochemistry of Plants, Leibniz University Hannover, Germany., Rhee S; Department of Agricultural Biotechnology, Seoul National University, Korea.; Research Institute of Agriculture and Life Sciences, Seoul National University, Korea.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2024 May; Vol. 291 (9), pp. 1992-2008. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1111/febs.17093
Abstrakt: The nucleoside inosine is a main intermediate of purine nucleotide catabolism in Saccharomyces cerevisiae and is produced via the dephosphorylation of inosine monophosphate (IMP) by IMP-specific 5'-nucleotidase 1 (ISN1), which is present in many eukaryotic organisms. Upon transition of yeast from oxidative to fermentative growth, ISN1 is important for intermediate inosine accumulation as purine storage, but details of ISN1 regulation are unknown. We characterized structural and kinetic behavior of ISN1 from S. cerevisiae (ScISN1) and showed that tetrameric ScISN1 is negatively regulated by inosine and adenosine triphosphate (ATP). Regulation involves an inosine-binding allosteric site along with IMP-induced local and global conformational changes in the monomer and a tetrameric re-arrangement, respectively. A proposed interaction network propagates local conformational changes in the active site to the intersubunit interface, modulating the allosteric features of ScISN1. Via ATP and inosine, ScISN1 activity is likely fine-tuned to regulate IMP and inosine homeostasis. These regulatory and catalytic features of ScISN1 contrast with those of the structurally homologous ISN1 from Plasmodium falciparum, indicating that ISN1 enzymes may serve different biological purposes in different organisms.
(© 2024 Federation of European Biochemical Societies.)
Databáze: MEDLINE
Externí odkaz: