posted on 2021-12-30, 14:34authored byJoseph
W. Schafer, Xi Chen, Steven D. Schwartz
Creating
efficient and stable enzymes for catalysis in pharmaceutical
and industrial laboratories is an important research goal. Arnold
et al. used directed evolution to engineer a natural tryptophan synthase
to create a mutant that is operable under laboratory conditions without
the need for a natural allosteric effector. The use of directed evolution
allows researchers to improve enzymes without understanding the structure–activity
relationship. Here, we present a transition path sampling study of
a key chemical transformation in the tryptophan synthase catalytic
cycle. We observed that while directed evolution does mimic the natural
allosteric effect from a stability perspective, fast protein dynamics
associated with chemistry has been dramatically altered. This work
provides further evidence of the role of protein dynamics in catalysis
and clearly demonstrates the multifaceted complexity of mutations
associated with protein engineering. This study also demonstrates
a fascinating contrast between allosteric and stand-alone functions
at the femtosecond time scale.