title: Coupling Protein Dynamics with Proton Transport in Human Carbonic Anhydrase II.
abstract: The role of protein dynamics in enzyme catalysis is one of the most highly debated topics in enzymology. The main controversy centers around what may be defined as functionally significant conformational fluctuations and how, if at all, these fluctuations couple to enzyme catalyzed events. To shed light on this debate, the conformational dynamics along the transition path surmounting the highest free energy barrier have been herein investigated for the rate limiting proton transport event in human carbonic anhydrase (HCA) II. Special attention has been placed on whether the motion of an excess proton is correlated with fluctuations in the surrounding protein and solvent matrix, which may be rare on the picosecond and subpicosecond time scales of molecular motions. It is found that several active site residues, which do not directly participate in the proton transport event, have a significant impact on the dynamics of the excess proton. These secondary participants are shown to strongly influence the active site environment, resulting in the creation of water clusters that are conducive to fast, moderately slow, or slow proton transport events. The identification and characterization of these secondary participants illuminates the role of protein dynamics in the catalytic efficiency of HCA II.
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, India.
authors.forename: Srabani
authors.initials: S
authors.lastname: Taraphder
authors.affiliation: Department of Chemical and Biological Engineering, Colorado School of Mines , 1500 Illinois Street, Golden, Colorado 80401, United States.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Maupin
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Frank Institute, and Computation Institute, University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.
authors.forename: Jessica M J
authors.initials: JM
authors.lastname: Swanson
authors.affiliation: Department of Chemistry, Institute for Biophysical Dynamics, James Frank Institute, and Computation Institute, University of Chicago , 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Voth
mesh_terms: D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics / Q000502:physiology; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D017136:Ion Transport / Q000502:physiology*; D008958:Models, Molecular; D009038:Motion; D009154:Mutation; D011487:Protein Conformation; D011522:Protons; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D011522:Protons; D012997:Solvents; D014867:Water; D024402:Carbonic Anhydrase II