title: Hydrogen tunneling links protein dynamics to enzyme catalysis.
abstract: The relationship between protein dynamics and function is a subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Here, we show how the quantum mechanical hydrogen tunneling associated with enzymatic C-H bond cleavage provides a unique window into the necessity of protein dynamics for achieving optimal catalysis. Experimental findings support a hierarchy of thermodynamically equilibrated motions that control the H-donor and -acceptor distance and active-site electrostatics, creating an ensemble of conformations suitable for H-tunneling. A possible extension of this view to methyl transfer and other catalyzed reactions is also presented. The impact of understanding these dynamics on the conceptual framework for enzyme activity, inhibitor/drug design, and biomimetic catalyst design is likely to be substantial.
authors.affiliation: Department of Chemistry, California Institute for Quantitative Sciences, University of California, Berkeley, California 94720, USA. klinman@berkeley.edu
authors.forename: Judith P
authors.initials: JP
authors.lastname: Klinman
authors.forename: Amnon
authors.initials: A
authors.lastname: Kohen
mesh_terms: D002384:Catalysis; D004798:Enzymes / Q000737:chemistry / Q000502:physiology*; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D011506:Proteins; D006859:Hydrogen