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Predicting Catalyst Extrudate Breakage Based on the Modulus of Rupture
Published on: May 13, 2018
Heavy Enzymes and the Rational Redesign of Protein Catalysts
Alan F Scott1, Louis Y-P Luk1, Iñaki Tuñón2
1School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK.
Abstract:
An unsolved mystery in biology concerns the link between enzyme catalysis and protein motions. Comparison between isotopically labelled "heavy" dihydrofolate reductases and their natural-abundance counterparts has suggested that the coupling of protein motions to the chemistry of the catalysed reaction is minimised in the case of hydride transfer. In alcohol dehydrogenases, unnatural, bulky substrates that induce additional electrostatic rearrangements of the active site enhance coupled motions. This finding could provide a new route to engineering enzymes with altered substrate specificity, because amino acid residues responsible for dynamic coupling with a given substrate present as hotspots for mutagenesis. Detailed understanding of the biophysics of enzyme catalysis based on insights gained from analysis of "heavy" enzymes might eventually allow routine engineering of enzymes to catalyse reactions of choice.
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