This talk will focus on 2 specific areas which both illuminate the importance (or lack thereof) of rapid protein dynamics on catalysis. The first is a comparative study of two evolutionarily distinct lactate dehydrogenase enzymes that catalyze the same chemistry but employ protein dynamics in different ways. The second area will focus on the design of artificial purine nucleoside phosphorylase enzymes. This was a prototypical enzyme that demonstrated a “heavy enzyme” effect – i.e. slowed local dynamics caused mistiming in critical promoting vibrations. This resulted in decreased on enzyme chemistry. We investigate whether we are able to “repair” this heavy enzyme deficit through targeted heavy amino acid mutations. This work is an experimental (Schramm – AECOM) theoretical collaboration (Schwartz – Arizona).<br/> <br/>One of the great mysteries of enzyme design is how active sites and protein dynamics are so perfectly optimized when chemistry rarely is the rate-limiting step in chemical turnover of enzymes. Addressing the evolutionary question begins to answer this conundrum, while at the same time, artificial enzyme design requires the proper design targets if they are to achieve catalysis at all. <br/>

Evolution and designing enzymes for rapid protein dynamics and catalysis

253rd National Meeting (2017)

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