Cooperativity and Specificity in Enzyme Kinetics: A Single-Molecule Time-based Perspective
Hong Qian 1*
1 University of Washington
* To whom correspondence should be addressed. E-mail: qian{at}amath.washington.edu.
Submitted on February 21, 2008
Revised on March 24, 2008
Accepted on 17 April 2008
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Abstract |
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An alternative theoretical approach to enzyme kinetics that is particularly applicable to single molecule enzymology is presented. The theory, originated by Van Slyke and Cullen in 1914, develops enzyme kinetics from a "time perspective" rather than the traditional "rate perspective", and emphasizes the nonequilibrium steady state nature of enzymatic reactions and the significance of small copy numbers of enzyme molecules in living cells. Sigmoidal cooperative substrate binding to slowly fluctuating, monomeric enzymes is shown to arise from association pathways with very small probability but extremely long passage time, which would be disregarded in the traditional rate perspective: A single enzyme stochastically takes alternative pathways in serial order rather than different pathways in parallel. The theory unifies dynamic cooperativity and Hopfield-Ninio's kinetic proofreading mechanism for specificity amplification.
Key Words:
dynamic cooperativity, hysteretic enzyme, kinetic proofreading, mean first passage time, nonequilibrium steady state, signaling network
