Analyzing In Silico the Relationship Between the Activation of the Edema Factor and Its Interaction With Calmodulin

Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of Bacilllus anthracis and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternate...

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Published in:Frontiers in molecular biosciences Vol. 7; p. 586544
Main Authors: Pitard, Irène, Monet, Damien, Goossens, Pierre L., Blondel, Arnaud, Malliavin, Thérèse E.
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media 04.12.2020
Frontiers Media S.A
Subjects:
allostery
Bacillus anthracis
Biochemistry, Molecular Biology
Bioinformatics
Biophysics
Cavity detection
Computer Science
Life Sciences
Molecular Biosciences
protein-protein interaction
Structural Biology
virulence factor
Bacillus anthracis
protein-protein interaction
virulence factor
Cavity detection
allostery
ISSN:2296-889X, 1662-5099, 2296-889X, 1662-5099
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Summary:Molecular dynamics (MD) simulations have been recorded on the complex between the edema factor (EF) of Bacilllus anthracis and calmodulin (CaM), starting from a structure with the orthosteric inhibitor adefovir bound in the EF catalytic site. The starting structure has been destabilized by alternately suppressing different co-factors, such as adefovir ligand or ions, revealing several long-distance correlations between the conformation of CaM, the geometry of the CaM/EF interface, the enzymatic site and the overall organization of the complex. An allosteric communication between CaM/EF interface and the EF catalytic site, highlighted by these correlations, was confirmed by several bioinformatics approaches from the literature. A network of hydrogen bonds and stacking interactions extending from the helix V of of CaM, and the residues of the switches A, B and C, and connecting to catalytic site residues, is a plausible candidate for the mediation of allosteric communication. The greatest variability in volume between the different MD conditions was also found for cavities present at the EF/CaM interface and in the EF catalytic site. The similarity between the predictions from literature and the volume variability might introduce the volume variability as new descriptor of allostery.
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Reviewed by: Sony Malhotra, Birkbeck, University of London, United Kingdom; Igor N. Berezovsky, Bioinformatics Institute (A*STAR), Singapore
Edited by: Agnel Praveen Joseph, Science and Technology Facilities Council, United Kingdom
This article was submitted to Biological Modeling and Simulation, a section of the journal Frontiers in Molecular Biosciences
ISSN:2296-889X
1662-5099
2296-889X
1662-5099
DOI:10.3389/fmolb.2020.586544