Document Detail

Effect of mutation K85R on GSK-3beta: Molecular dynamics simulation.
MedLine Citation:
PMID:  18955029     Owner:  NLM     Status:  MEDLINE    
As a serine-threonine protein kinase, glycogen synthase kinase-3 (GSK-3) regulates the synthesis of glycogen and plays important roles in several signaling pathways. It is a key therapeutic target for a number of diseases, such as diabetes, cancer, Alzheimer's disease and chronic inflammation. The conserved Lys85 is important to GSK-3beta activity and in this paper we illustrate the significant role of Lys85 using dynamic simulation. We find that when Lys85 is mutated to Arg, one of the two conserved hydrogen bonds between Lys85 and ATP disappears, the salt bridge between Lys85 and Glu97 cannot form, and conformational changes of Phe93, Arg96 and Glu211 occur. These will cause conformational changes of the substrate binding groove that would inhibit the activity of GSK-3beta. MM-GBSA calculations reveal that the K85R mutation could lead to a less energy-favorable complex, which is consistent with the structural analysis.
Hao Sun; Yong-jun Jiang; Qing-sen Yu; Cheng-cai Luo; Jian-wei Zou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-26
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  377     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2008-12-15     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  962-5     Citation Subset:  IM    
Department of Chemistry, Zhejiang University, Hangzhou, 310027, Zhejiang Province, PR China.
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MeSH Terms
Adenosine Triphosphate / chemistry
Amino Acid Substitution
Arginine / chemistry*,  genetics
Computer Simulation*
Glycogen Synthase Kinase 3 / antagonists & inhibitors,  chemistry*,  genetics*
Lysine / chemistry*,  genetics
Models, Chemical*
Protein Conformation
Reg. No./Substance:
56-65-5/Adenosine Triphosphate; 56-87-1/Lysine; 74-79-3/Arginine; EC synthase kinase 3 beta; EC Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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