Louisiana State University School of Medicine & Health Sciences Center, USA
Sunyoung Kim has completed her PhD at the University of Michigan and the University of Padova, Italy and Post-doctoral studies at the University of Minnesota. She is a Member of the Louisiana Cancer Research Consortium and Founder of a spin-out company to personalize medicine with structural biomarkers. She leads a collaborative, multilab nanomotor research program. She has published more than 25 papers and serves as an Editorial Board Member of the Journal of Biological Chemistry. In addition, she has performed a variety of administrative roles at the departmental, institutional and state levels, as well as held elected positions for national scientific societies.
ATP hydrolysis requires that a proton f rom the water nucleophile must be abstr acted and transferred in order to create a hydroxide capable of attacking the substrate. In crystallographic capture of ATP hydrolysis, a two-water cluster is found in the active site of two diffe rent kinesin isoforms. These data suggest that a proton is shared between the lytic water , positioned for gamma-phosphate attack, and the second water that serves as a general base. The unusual short distance between the two orthosteric water molecules , observed by crystallography, is confirmed by solvent kinetic isotope experiments. The positive kinetic isotope e ffect (KIE) confirms proton abstraction from water commits kinesin to catalysis and its pH-dependence verifies that switch salt-bridge residues direct chemotransduction . Additionally, a classical descr iption for this proton transfer is refuted by the KIE magnitude, tempe rature-independent Arrhenius pre-exponential fa ctor rati os, and activation energy differences. Taken together, we conclude that the first step in kinesin catalysis has a tunneling component, a quantum mechanical event by which a particle transfers through a reaction barrier. This first detection of tunneling in an ATPase is of consequence for two reasons. First, proton tunneling is likely widespread in biomolecules, rather than solely a characteristic of metalloenzymes. Second, energy barrier penetration by proton tunneling is an alternate explanation to classical transition-state stabilization theory for the fast reactivities of motor proteins.