I am Steve Benkovic and I hold the Eberly Chair in Chemistry at Penn State.
To begin, I'd like to update my previous lecture on Biological Catalysis.
I plan to review sufficient background material to serve as
a basis for my discussion of the recent advances that have further informed this topic.
The illustration presents the reaction cycle for DHFR,
more about that later.
A feature of enzymes is the rate accelerations,
relative to their reaction, solution,
counterpart, with their ratios being in the millions.
I wish to explore three questions.
They are, how do enzyme motions and fluctuations impact catalysis?
We know that the structures of enzymes are dynamic,
but how do these dynamic features actually impact catalysis?
Are the time scales for
protein structural changes and the enzymatic catalytic cycle similar?
We will review the time scales for protein motions in the later slide.
And the third question is,
how are electrostatics modulated in enzyme active sites in conjunction with catalysis?
Such interactions long have been implicated in catalysis,
but how are they optimized?
Remember, we still view catalysis in terms of transition state theory.
The key being selective stabilization of the transition state,
lowering the free energy barrier that,
in turn, translates into an increased reaction rate.