Document Detail

Understanding the basis of a class of paradoxical mutations in AraC through simulations.
MedLine Citation:
PMID:  23150197     Owner:  NLM     Status:  MEDLINE    
Most mutations at position 15 in the N-terminal arm of the regulatory protein AraC leave the protein incapable of responding to arabinose and inducing the proteins required for arabinose catabolism. Mutations at other positions of the arm do not have this behavior. Simple energetic analysis of the interactions between the arm and bound arabinose do not explain the uninducibility of AraC with mutations at position 15. Extensive molecular dynamics (MD) simulations, carried out largely on the Open Science Grid, were done of the wild-type protein with and without bound arabinose and of all possible mutations at position 15, many of which were constructed and measured for this work. Good correlation was found for deviation of arm position during the simulations and inducibility as measured in vivo of the same mutant proteins. Analysis of the MD trajectories revealed that preservation of the shape of the arm is critical to inducibility. To maintain the correct shape of the arm, the strengths of three interactions observed to be strong in simulations of the wild-type AraC protein need to be preserved. These interactions are between arabinose and residue 15, arabinose and residues 8-9, and residue 13 and residue 15. The latter interaction is notable because residues L9, Y13, F15, W95, and Y97 form a hydrophobic cluster which needs to be preserved for retention of the correct shape.
Ana Damjanovic; Benjamin T Miller; Robert Schleif
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-12-24
Journal Detail:
Title:  Proteins     Volume:  81     ISSN:  1097-0134     ISO Abbreviation:  Proteins     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-08-02     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  United States    
Other Details:
Languages:  eng     Pagination:  490-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Amino Acid Substitution
AraC Transcription Factor / chemistry*,  genetics
Arabinose / chemistry
Enzyme Induction
Escherichia coli / chemistry,  genetics
Escherichia coli Proteins / chemistry*,  genetics
Genetic Vectors / chemistry
Hydrophobic and Hydrophilic Interactions
Isomerases / chemistry
Molecular Dynamics Simulation*
Protein Conformation
Protein Folding
Protein Interaction Mapping
Protein Multimerization
Protein Structure, Tertiary
Grant Support
Z01 HL001050-10/HL/NHLBI NIH HHS
Reg. No./Substance:
0/AraC Transcription Factor; 0/AraC protein, E coli; 0/Escherichia coli Proteins; B40ROO395Z/Arabinose; EC 5.-/Isomerases

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