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Tytuł pozycji:

Targeting protein conformations with small molecules to control protein complexes.

Tytuł:
Targeting protein conformations with small molecules to control protein complexes.
Autorzy:
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.
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: .
Źródło:
Trends in biochemical sciences [Trends Biochem Sci] 2022 Dec; Vol. 47 (12), pp. 1023-1037. Date of Electronic Publication: 2022 Aug 16.
Typ publikacji:
Journal Article; Review; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: Cambridge (Eng) : Elsevier Trends Journals
Original Publication: Amsterdam, Published for the International Union of Biochemistry by Elsevier Scientific Pub. Co.
MeSH Terms:
Proteins*/chemistry
Drug Discovery*
Protein Conformation
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Grant Information:
R01 CA178394 United States CA NCI NIH HHS; R01 CA238229 United States CA NCI NIH HHS; P30 AG038072 United States AG NIA NIH HHS; P30 CA013330 United States CA NCI NIH HHS; P01 AG031782 United States AG NIA NIH HHS
Contributed Indexing:
Keywords: activators; conformational plasticity; dynamic protein complexes; inhibitors; protein–protein interactions
Substance Nomenclature:
0 (Proteins)
Entry Date(s):
Date Created: 20220819 Date Completed: 20221115 Latest Revision: 20231202
Update Code:
20240104
PubMed Central ID:
PMC9669135
DOI:
10.1016/j.tibs.2022.07.002
PMID:
35985943
Czasopismo naukowe
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.
Competing Interests: Declaration of interests None declared by authors.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)

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