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Toxins 2017, 9(7), 199; doi:10.3390/toxins9070199

Molecular Modeling of the Catalytic Domain of CyaA Deepened the Knowledge of Its Functional Dynamics

Institut Pasteur and CNRS UMR 3528, Unité de Bioinformatique Structurale, 28, rue du Dr Roux, F-75015 Paris, France
Received: 13 May 2017 / Revised: 21 June 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
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Abstract

Although CyaA has been studied for over three decades and revealed itself to be a very good prototype for developing various biotechnological applications, only a little is known about its functional dynamics and about the conformational landscape of this protein. Molecular dynamics simulations helped to clarify the view on these points in the following way. First, the model of interaction between AC and calmodulin (CaM) has evolved from an interaction centered on the surface between C-CaM hydrophobic patch and the α helix H of AC, to a more balanced view, in which the C-terminal tail of AC along with the C-CaM Calcium loops play an important role. This role has been confirmed by the reduction of the affinity of AC for calmodulin in the presence of R338, D360 and N347 mutations. In addition, enhanced sampling studies have permitted to propose a representation of the conformational space for the isolated AC. It remains to refine this representation using structural low resolution information measured on the inactive state of AC. Finally, due to a virtual screening study on another adenyl cyclase from Bacillus anthracis, weak inhibitors of AC have been discovered. View Full-Text
Keywords: Bordetella pertussis; adenyl cyclase; molecular dynamics simulation; enhanced sampling; virtual screening; thiophen ureoacids Bordetella pertussis; adenyl cyclase; molecular dynamics simulation; enhanced sampling; virtual screening; thiophen ureoacids
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Malliavin, T.E. Molecular Modeling of the Catalytic Domain of CyaA Deepened the Knowledge of Its Functional Dynamics. Toxins 2017, 9, 199.

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