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

verfasst von: 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.
Organisationseinheit(en): Institut für Pflanzenernährung
Externe Organisation(en): Seoul National University
Typ: Artikel
Journal: FEBS Journal
Band: 291
Seiten: 1992-2008
Anzahl der Seiten: 17
ISSN: 1742-464X
Publikationsdatum: 16.02.2024
Publikationsstatus: Elektronisch veröffentlicht (E-Pub)
Peer-reviewed: Ja
ASJC Scopus Sachgebiete: Biochemie, Molekularbiologie, Zellbiologie
Elektronische Version(en): https://doi.org/10.1111/febs.17093 (Zugang: Geschlossen)

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 = "Funding Information: We would like to thank Dr Eunyoung Park and Prof Jeong‐Han Kim for HPLC measurements at the early stage of a project. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2021R1A2C2092118 and RS‐2023‐00207820). ",
year = "2024",
month = feb,
day = "16",
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",
}