Conformational Coupling in DNA Polymerase Information Transfer [and Discussion]

The extraordinary fidelity of DNA replication during forward polymerization and exonuclease error correction is largely a function of a conformational change that occurs in response to a correct dNTP binding to properly base-paired duplex DNA. The conformational change serves as a kinetic barrier to effect the rapid incorporation of correct bases while minimizing the rate of polymerization with incorrect bases and allowing for selective removal of mismatches. However, in spite of the number of attractive features to the conformational change model, the evidence in support of such a rate-limiting step is still subject to significant uncertainty. It is the challenge of further work on DNA polymerases as well as many other enzyme systems to devise new methods to define the transient state of the enzyme during catalysis and to relate the kinetic and thermodynamic parameters to the enzyme structure.