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Heavy Enzymes and the Rational Redesign of Protein Catalysts
Author(s) -
Scott Alan F.,
Luk Louis Y.P.,
Tuñón Iñaki,
Moliner Vicent,
Allemann Rudolf K.
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900134
Subject(s) - protein engineering , enzyme , chemistry , enzyme catalysis , substrate (aquarium) , catalysis , biocatalysis , active site , alcohol dehydrogenase , mutagenesis , biochemistry , combinatorial chemistry , stereochemistry , biology , reaction mechanism , ecology , gene , mutation
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.