Warncke Lab Research
Entropic Origin of Cobalt-Carbon Bond Cleavage Catalysis in a B12 Enzyme
Prof. Kurt Warncke and former grad student, Dr. Miao Wang, demonstrate that bond cleavage catalysis in the EAL enzyme originates from a large, favorable activation entropy, which represents a paradigm shift from previous proposals. A protein configurational catalysis mechanism is proposed.
"The cleavage of the cobalt-carbon bond of the bound adenosylcobalamin cofactor unleashes a sequence of highly-reactive, unpaired electron intermediates (radicals) that are productively channeled by B12-dependent enzymes. We were able to measure the bond cleavage kinetics in the EAL enzyme, at low temperatures in a fluid cryosolvent system, by using time-resolved, full-spectrum electron paramagnetic resonance (EPR) spectroscopy. The results reveal that bond cleavage catalysis in EAL originates from a large, favorable activation entropy, which represents a paradigm shift from previous enthalpy-based proposals. A "configurational catalysis" mechanism is proposed, in which the favorable activation entropy arises from ramification of protein configurations along the reaction coordinate." - Prof. Warncke
This research was published in: 10.1021/ja404467d J. Am. Chem. Soc., 135, 15077-15084 (2013) - Abstract