Linked Life Data

21328310

Source:http://linkedlifedata.com/resource/pubmed/id/21328310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-4-26
pubmed:abstractText
GSK3? plays an important role in many physiological functions; dysregulated GSK3? is involved in human diseases such as diabetes, cancer, and Alzheimer's disease. This study uses MD simulations to determine the interaction between GSK3? and a peptide derived from GSKIP, a novel GSK3? interacting protein. Results show that GSKIPtide is inlaid in a binding pocket consisting of an ?-helix and an extended loop near the carboxy-terminal end. This binding pocket is hydrophobic, and is responsible for the protein-protein interaction of two other GSK3? interacting proteins: FRAT and Axin. The GSKIPtide binding mode is closer to that of AxinGID (in the Axin-GSK3-interacting domain). The single-point mutations of V267G and Y288F in GSK3? differentiate the binding modes between GSK3 and GSKIPtide, AxinGID, and FRATide. The V2677G mutation of GSK3? reduces the GSKIPtide binding affinity by 70% and abolishes the binding affinity with AxinGID, but has no effect on FRATide. However, GSK3? Y288F completely abolishes the FRATide binding without affecting GSKIPtide or AxinGID binding. An analysis of the GSK3?-GSKIPtide complex structure and the X-ray crystal structures of GSK3?-FRATide and GSK3?-AxinGID complexes suggests that the hydroxyl group of Y288 is crucial to maintaining a hydrogen bond network in GSK3?-FRATide. The hydrophobic side chain of V267 maintains the integrity of helix-helix ridge-groove hydrophobic interaction for GSK3?-GSKIPtide and GSK3?-AxinGID. This study simulates these two mutant systems to provide atomic-level evidence of the aforementioned experimental results and validate the wild-type complex structure prediction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3525
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Wiley Periodicals, Inc., a Wiley company.
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
461-71
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Prediction of the binding mode between GSK3? and a peptide derived from GSKIP using molecular dynamics simulation.
pubmed:affiliation
Department of Internal Medicine, Zuoying Armed Forces General Hospital, Kaohsiung, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't