Protonation states of remote residues affect binding-release dynamics of the ligand but not the conformation of apo ferric binding protein

Warning The system is temporarily closed to updates for reporting purpose.

Güven, Gökçe and Atılgan, Ali Rana and Atılgan, Canan (2014) Protonation states of remote residues affect binding-release dynamics of the ligand but not the conformation of apo ferric binding protein. Journal of Physical Chemistry B, 118 (40). pp. 11677-11687. ISSN 1520-6106 (Print) 1520-5207 (Online)

[thumbnail of 2014_jcpB.pdf] PDF
2014_jcpB.pdf
Restricted to Registered users only

Download (3MB) | Request a copy

Abstract

We have studied the apo (Fe3+ free) form of periplasmic ferric binding protein (FbpA) under different conditions and we have monitored the changes in the binding and release dynamics of H2PO4 that acts as a synergistic anion in the presence of Fe3+. Our simulations predict a dissociation constant in agreement with the experimentally measured value under the same ionic pH conditions. We apply perturbations relevant for changes in environmental conditions as (i) different values of ionic strength and (ii) protonation of a group of residues to mimic a different pH environment. Local perturbations are also studied by protonation or mutation of a site distal to the binding region that is known to mechanically manipulate the hinge-like motions of FbpA. We find that while the average conformation of the protein is intact in all simulations, the H2PO4 binding constant is substantially altered by the changing conditions. In particular, the bound fraction which is 20% for the wild type system is increased to 50% with a D52A mutation/protonation and further to over 90% at the protonation conditions mimicking those at pH 5.5. The change in the dynamics is traced to the altered electrostatic potential distribution on the surface of the protein which in turn affects hydrogen bonding patterns at the active site. The observations are also quantified by rigorous free energy calculations. Our results lend clues as to how the environment versus single residue perturbations may be utilized for regulation of binding modes in hFbpA systems in the absence of conformational changes.
Item Type: Article
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Materials Science & Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Canan Atılgan
Date Deposited: 22 Dec 2014 10:49
Last Modified: 02 Aug 2019 14:43
URI: https://research.sabanciuniv.edu/id/eprint/25585

Actions (login required)

View Item
View Item