Targeting protein conformations with small molecules to control protein complexes.

Protein Conformation Proteins / chemistry Drug Discovery
activators conformational plasticity dynamic protein complexes inhibitors protein–protein interactions

Journal

Trends in biochemical sciences
ISSN: 0968-0004
Titre abrégé: Trends Biochem Sci
Pays: England
ID NLM: 7610674

Informations de publication

Date de publication:
12 2022
Historique:
received: 26 02 2022
revised: 23 06 2022
accepted: 11 07 2022
pubmed: 20 8 2022
medline: 16 11 2022
entrez: 19 8 2022
Statut: ppublish

Résumé

Dynamic protein complexes function in all cellular processes, from signaling to transcription, using distinct conformations that regulate their activity. Conformational switching of proteins can turn on or off their activity through protein-protein interactions, catalytic function, cellular localization, or membrane interaction. Recent advances in structural, computational, and chemical methodologies have enabled the discovery of small-molecule activators and inhibitors of conformationally dynamic proteins by using a more rational design than a serendipitous screening approach. Here, we discuss such recent examples, focusing on the mechanism of protein conformational switching and its regulation by small molecules. We emphasize the rational approaches to control protein oligomerization with small molecules that offer exciting opportunities for investigation of novel biological mechanisms and drug discovery.

Identifiants

DOI: 10.1016/j.tibs.2022.07.002 PMID: 35985943 PMC: PMC9669135
pubmed: 35985943
pii: S0968-0004(22)00184-0
doi: 10.1016/j.tibs.2022.07.002
pmc: PMC9669135
mid: NIHMS1824007
pii:
doi:

Substances chimiques

Proteins 0

Types de publication

Journal Article Review Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1023-1037

Subventions

Organisme : NCI NIH HHS
ID : R01 CA178394
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA238229
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG038072
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG031782
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests None declared by authors.

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Auteurs

Emmanouil Zacharioudakis (E)

Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.

Evripidis Gavathiotis (E)

Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: evripidis.gavathiotis@einsteinmed.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Targeting protein conformations with small...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Targeting protein conformations with small...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Targeting protein conformations with small...