Ligands Turning Around in the Midst of Protein Conformers: The Origin of Ligand-Protein Mating. A NMR View

T.      A. Pertinhez; A.      Spisni

doi:10.2174/156802611794863535

Abstract

Protein-ligand binding is a puzzling process. Many theories have been devised since the pioneering key-and-lock hypothesis based on the idea that both the protein and the ligand have a rigid single conformation. Indeed, molecular motion is the essence of the universe. Consequently, not only proteins are characterized by an extraordinary conformational freedom, but ligands too can fluctuate in a rather vast conformational space. In this scenario, the quest to understand how do they match is fascinating. Recognizing that the inherent dynamics of molecules is the key factor controlling the success of binding and, subsequently, of their chemical/biological function, here we present a view of this process from the NMR stand point. A description of the most relevant NMR parameters that can provide insights, at atomic level, on the mechanisms of protein- ligand binding is provided in the final section.

Keywords: NMR, ligand binding, protein, conformation, flexibility, bound/unbound states, ligand, nduced-fit model, reactivity, X-ray crystallography became, MWC, equilibrium, per-turbation, conformational selection model, NMR spectroscopy, heterogeneity, CRABPI, cytidylyl-transferase en-zyme, 15N, rigidification, SRLS, NH bonds, MUP I, hemophore, S2, RDCs, Calmodulin, ubiquitous protein, signal transduction, NOE, CaM-MLCK, fine tuning, PRE, enzyme 1, CRBP, Enzymes, DHFR, cofactor, substrate, PDF, NAMFIS, HSQC, h3JNC, tr-NOE, STD, R1, (R2) a, Rex, CRBP type I, Paramagnetic Mapping, PCS, probability distribution of states