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

authored by: Sujeong Byun, Changkon Park, Jeong Yong Suh, Claus Peter Witte, Sangkee Rhee
Abstract: 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.
Organisation(s): Institute of Plant Nutrition
External Organisation(s): Seoul National University
Type: Article
Journal: FEBS Journal
Volume: 291
Pages: 1992-2008
No. of pages: 17
ISSN: 1742-464X
Publication date: 03.05.2024
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Biochemistry, Molecular Biology, Cell Biology
Electronic version(s): https://doi.org/10.1111/febs.17093 (Access: Closed)

BibTeX

@article{93e0b1a9d30b452a9eee327a96b9a24f,
title = "Structure, cooperativity and inhibition of the inosine 5′-monophosphate-specific phosphatase from Saccharomyces cerevisiae",
abstract = "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.",
keywords = "allosteric site, ATP, inosine, negative regulation, purine metabolism",
author = "Sujeong Byun and Changkon Park and Suh, {Jeong Yong} and Witte, {Claus Peter} and Sangkee Rhee",
note = "Publisher Copyright: {\textcopyright} 2024 Federation of European Biochemical Societies.",
year = "2024",
month = may,
day = "3",
doi = "10.1111/febs.17093",
language = "English",
volume = "291",
pages = "1992--2008",
journal = "FEBS Journal",
issn = "1742-464X",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "9",
}