Modulation of the Conformational Dynamics of Apo-Adenylate Kinase through a π–Cation Interaction
| Autor: | Biman Jana, Ritaban Halder, Sandipan Chakraborty, Rabindra Nath Manna |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein Conformation Population Adenylate kinase Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Molecular mechanics 03 medical and health sciences Closed state Cations Modulation (music) Escherichia coli Materials Chemistry Physical and Theoretical Chemistry education education.field_of_study Chemistry Adenylate Kinase Dynamics (mechanics) 0104 chemical sciences Surfaces Coatings and Films ADK Crystallography 030104 developmental biology Catalytic cycle Quantum Theory |
| Zdroj: | The Journal of Physical Chemistry B. 121:5699-5708 |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.7b01736 |
| Popis: | Large-scale conformational transition from open to closed state of adenylate kinase (ADK) is essential for its catalytic cycle. Apo-ADK undergoes conformational transition in a way that closely resembles an open-to-closed conformational transition. Here, equilibrium simulations, free-energy simulations, and quantum mechanics/molecular mechanics (QM/MM) calculations in combination with several bioinformatics approaches have been used to explore the molecular origin of this conformational transition in apo-ADK. In addition to its conventional open state, Escherichia coli apo-ADK adopts conformations that resemble a closed-like intermediate, the "half-open-half-closed" (HOHC) state, and a π-cation interaction can account for the stability of this HOHC state. Energetics and the electronic properties of this π-cation interaction have been explored using QM/MM calculations. Upon rescinding the π-cation interaction, the conformational landscape of the apo-ADK changes completely. The apo-ADK population is shifted completely toward the open state. This π-cation interaction is highly conserved in bacterial ADK; the cationic guanidinium moiety of a conserved ARG interacts with the delocalized π-electron cloud of either PHE or TYR. Interestingly, this study demonstrates the modulation of a principal protein dynamics by a conserved specific π-cation interaction across different organisms. |
| Databáze: | OpenAIRE |
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