Hydrogen tunneling links protein dynamics to enzyme catalysis

• Published in: Annual review of biochemistry Vol. 82; p. 471
• Main Authors: Klinman, Judith P, Kohen, Amnon
• Format: Journal Article
• Language: English
• Published: United States 01.01.2013
• Subjects: Catalysis; Enzymes - chemistry; Enzymes - physiology; Hydrogen - chemistry; Hydrogen - metabolism; Hydrogen - physiology; Kinetics; Models, Molecular; Protein Conformation; Proteins - chemistry; Proteins - physiology; Thermodynamics
• ISSN: 1545-4509
• DOI: 10.1146/annurev-biochem-051710-133623

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.