Allosteric pluripotency: challenges and opportunities.

Allosteric Regulation / physiology Allosteric Site Cyclic AMP-Dependent Protein Kinases Drug Design Signal Transduction
agonism allosteric regulation antagonism cAMP kinases protein kinase A

Journal

The Biochemical journal
ISSN: 1470-8728
Titre abrégé: Biochem J
Pays: England
ID NLM: 2984726R

Informations de publication

Date de publication:
14 04 2022
Historique:
received: 21 11 2021
revised: 17 03 2022
accepted: 21 03 2022
entrez: 11 4 2022
pubmed: 12 4 2022
medline: 13 4 2022
Statut: ppublish

Résumé

Allosteric pluripotency arises when the functional response of an allosteric receptor to an allosteric stimulus depends on additional allosteric modulators. Here, we discuss allosteric pluripotency as observed in the prototypical Protein Kinase A (PKA) as well as in other signaling systems, from typical multidomain signaling proteins to bacterial enzymes. We identify key drivers of pluripotent allostery and illustrate how hypothesizing allosteric pluripotency may solve apparent discrepancies currently present in the literature regarding the dual nature of known allosteric modulators. We also outline the implications of allosteric pluripotency for cellular signaling and allosteric drug design, and analyze the challenges and opportunities opened by the pluripotent nature of allostery.

Identifiants

DOI: 10.1042/BCJ20210528 PMID: 35403669
pubmed: 35403669
pii: 231129
doi: 10.1042/BCJ20210528
doi:

Substances chimiques

Cyclic AMP-Dependent Protein Kinases EC 2.7.11.11

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

825-838

Subventions

Organisme : CIHR
ID : 389522
Pays : Canada

Informations de copyright

© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Auteurs

Madoka Akimoto (M)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

Karla Martinez Pomier (K)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

Bryan VanSchouwen (B)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

Jung Ah Byun (JA)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

Mariia Khamina (M)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

Giuseppe Melacini (G)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
ORCID: 0000-0003-1164-2853

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Régulation allostérique › Allosteric pluripotency: challenges and opportunities.
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Site allostérique › Allosteric pluripotency: challenges and opportunities.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Cyclic Nucleotide-Regulated Protein Kinases › Cyclic AMP-Dependent Protein Kinases › Allosteric pluripotency: challenges and opportunities.
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Conception de médicament › Allosteric pluripotency: challenges and opportunities.
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Allosteric pluripotency: challenges and opportunities.