01750nas a2200157   4500008004100000022001400041245012100055210006900176260000900245300001400254490000700268520114400275100001801419700002301437856013201460       2020                        eng d  a1948-718500aProtonation-induced dynamic allostery in PDZ domain: evidence of perturbation-independent universal response network0 aProtonationinduced dynamic allostery in PDZ domain evidence of p  cNOV   a9026-90310 v113 a<p>Dynamic allostery is a relatively new paradigm where certain external perturbations may lead to modulation of conformational dynamics at a distant part of a protein without significant changes in the overall structure. While most well-characterized examples of dynamic allostery involve binding with other entities like small molecules, peptides, or nucleic acids, in this work we demonstrate that chemical modifications like protonation may lead to significant dynamical allosteric response in a PDZ domain protein. Tuning the protonation states of two histidine residues (H317 and H372), we identify the allosteric pathways responsible for the dynamic response. Interestingly, the same set of residues that constitute the allosteric response network upon ligand binding seem to be responsible for protonation-induced dynamic allostery. Thus, we propose the existence of an inherent universal response network in signaling proteins, where the same set of residues can respond to varying types of external perturbations in terms of rearrangement of hydrogen-bonded network and redistribution of electrostatic interaction energies.</p>
1 aKumawat, Amit1 aChakrabarty, Suman  uhttps://library.ncl.res.in/content/protonation-induced-dynamic-allostery-pdz-domain-evidence-perturbation-independent-universal