| Insights into Protein - DNA Interactions, Stability and Allosteric Communications: A Computational Study of Muts Alpha-DNA Recognition Complexes. | |
| | |
MedLine Citation:
|
PMID: 22208277 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
DNA mismatch repair proteins (MMR) maintain genetic stability by recognizing and repairing mismatched bases and insertion/deletion loops mistakenly incorporated during DNA replication, and initiate cellular response to certain types of DNA damage. Loss of MMR in mammalian cells has been linked to resistance to certain DNA damaging chemotherapeutic agents, as well as to increase risk of cancer. Mismatch repair pathway is considered to involve the concerted action of at least 20 proteins. The most abundant MMR mismatch-binding factor in eukaryotes, MutS_, recognizes and initiates the repair of base-base mismatches and small insertion/deletion. We performed molecular dynamics simulations on mismatched and damaged MutS_-DNA complexes. A comprehensive DNA binding site analysis of relevant conformations shows that MutS_ proteins recognize the mismatched and platinum cross-linked DNA substrates in significantly different modes. Distinctive conformational changes associated with MutS_ binding to mismatched and damaged DNA have been identified and they provide insight into the involvement of MMR proteins in DNA-repair and DNA-damage pathways. Stability and allosteric interactions at the heterodimer interface associated with the mismatch and damage recognition step allow for prediction of key residues in MMR cancer-causing mutations. A rigorous hydrogen bonding analysis for ADP molecules at the ATPase binding sites is also presented. Due to extended number of known MMR cancer causing mutations among the residues proved to make specific contacts with ADP molecules, recommendations for further studies on similar mutagenic effects were made. |
| | |
Authors:
|
L Negureanu; F R Salsbury |
Related Documents
:
|
21659837 - Dna collection from used toothbrushes as a means to decedent identification. 22213487 - Comparison of dna apoptosis in mouse and human blastocysts after vitrification and slow... 21791887 - Bartonella species in wild rodents and the infested fleas in japan. 8263177 - Rapid identification of some leptospira isolates from cattle by random amplified polymo... 23754627 - Non-mrna 3' end formation: how the other half lives. 1390707 - Role of individual histone tyrosines in the formation of the nucleosome complex. |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Journal of biomolecular structure & dynamics Volume: 29 ISSN: 1538-0254 ISO Abbreviation: J. Biomol. Struct. Dyn. Publication Date: 2012 Feb |
Date Detail:
|
Created Date: 2012-01-02 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8404176 Medline TA: J Biomol Struct Dyn Country: United States |
Other Details:
|
Languages: eng Pagination: 757-76 Citation Subset: IM |
Affiliation:
|
Department of Physics, Wake Forest University, Winston Salem, NC 27106, USA. salsbufr@wfu.edu. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Dynamic and Structural Changes in the Minimally Restructuring EcoRI Bound to a Minimally Mutated DNA...
Next Document: Identification of the Structural Features that Mediate Binding Specificity in the Recognition of STA...