Enzymatic transition states and dynamic motion in barrier crossing.
What are the atomic motions at enzymatic catalytic sites on the timescale of chemical change? Combined experimental and computational chemistry approaches take advantage of transition-state analogs to reveal dynamic motions linked to transition-state formation. QM/MM transition path sampling from reactive complexes provides both temporal and dynamic information for barrier crossing. Fast (femtosecond to picosecond) dynamic motions provide essential links to enzymatic barrier crossing by local or promoting-mode dynamic searches through bond-vibrational space. Transition-state lifetimes are within the femtosecond timescales of bond vibrations and show no manifestations of stabilized, equilibrated complexes. The slow binding and protein conformational changes (microsecond to millisecond) also required for catalysis are temporally decoupled from the fast dynamic motions forming the transition state. According to this view of enzymatic catalysis, transition states are formed by fast, coincident dynamic excursions of catalytic site elements, while the binding of transition-state analogs is the conversion of the dynamic excursions to equilibrated states.
Schwartz
Steven D
SD
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA.
Schramm
Vern L
VL
D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D011683:Purine-Nucleoside Phosphorylase / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics; D013997:Time Factors; D014732:Vibration
D004798:Enzymes; D007770:L-Lactate Dehydrogenase; D011683:Purine-Nucleoside Phosphorylase