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PMID: 23582321 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Review

Allostery in disease and in drug discovery.

Cell ·Vol. 153 ·No. 2 ·2013-04-11 ·Pages 293-305

Nussinov R, Tsai CJ

Abstract

Allostery is largely associated with conformational and functional transitions in individual proteins. This concept can be extended to consider the impact of conformational perturbations on cellular function and disease states. Here, we clarify the concept of allostery and how it controls physiological activities. We focus on the challenging questions of how allostery can both cause disease and contribute to development of new therapeutics. We aim to increase the awareness of the linkage between disease symptoms on the cellular level and specific aberrant allosteric actions on the molecular level and to emphasize the potential of allosteric drugs in innovative therapies.

MeSH Terms
Allosteric Regulation Allosteric Site Animals Disease/genetics Drug Discovery Drug Therapy Enzymes Humans Models, Molecular Protein Conformation Protein Kinase Inhibitors/chemistry Protein Kinases/chemistry,genetics Signal Transduction Thermodynamics
Chemicals
Enzymes Protein Kinase Inhibitors Protein Kinases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nussinov Ruth
National Cancer Institute, Center for Cancer Research Nanobiology Program, Frederick National Laboratory for Cancer Research, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA. nussinor@helix.nih.gov
Tsai Chung-Jung
Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
Published
2013-04-11
Pages
293-305
Language
English
Region
United States
NLM ID
0413066
Subset
IM
Grants
PHS HHS · HHSN261200800001E · United States
Intramural NIH HHS · United States
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