Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 1992-2008 |
| Seitenumfang | 17 |
| Fachzeitschrift | FEBS Journal |
| Jahrgang | 291 |
| Ausgabenummer | 9 |
| Publikationsstatus | Veröffentlicht - 3 Mai 2024 |
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.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biochemie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Molekularbiologie
- Biochemie, Genetik und Molekularbiologie (insg.)
- Zellbiologie
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in: FEBS Journal, Jahrgang 291, Nr. 9, 03.05.2024, S. 1992-2008.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Structure, cooperativity and inhibition of the inosine 5′-monophosphate-specific phosphatase from Saccharomyces cerevisiae
AU - Byun, Sujeong
AU - Park, Changkon
AU - Suh, Jeong Yong
AU - Witte, Claus Peter
AU - Rhee, Sangkee
N1 - Publisher Copyright: © 2024 Federation of European Biochemical Societies.
PY - 2024/5/3
Y1 - 2024/5/3
N2 - 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.
AB - 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.
KW - allosteric site
KW - ATP
KW - inosine
KW - negative regulation
KW - purine metabolism
UR - http://www.scopus.com/inward/record.url?scp=85185258276&partnerID=8YFLogxK
U2 - 10.1111/febs.17093
DO - 10.1111/febs.17093
M3 - Article
C2 - 38362806
AN - SCOPUS:85185258276
VL - 291
SP - 1992
EP - 2008
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 9
ER -