title: The effect of the hydrophobic environment on the retro-aldol reaction: comparison to a computationally-designed enzyme.
abstract: Recent work on a computationally-designed retroaldolase RA-61 suggested that most of the rate-acceleration brought about by this enzyme was due to non-specific interactions with the aromatic substrate. To provide a benchmark for the role of non-specific interactions in this system, we measured the second-order rate constant for the amine-catalysed retro-aldol reaction of methodol in the presence of non-specific hydrophobic pockets such as micelles. We found that a simple micellar system, that consists of a positively-charged surfactant and a long-chain amine, can accelerate the retro-aldol reaction of methodol by 9500-fold. This effect rivals the 10(5)-fold rate acceleration of RA-61. Similar results were obtained with BSA used as the catalyst, implying that the retro-aldol reaction of methodol can be greatly accelerated by non-specific hydrophobic pockets that contain an amino group.
authors.affiliation: College of Charleston, Department of Chemistry and Biochemistry, 66 George Street, Charleston, SC 29424, USA. forconim@cofc.edu.
authors.forename: Joshua
authors.initials: J
authors.lastname: Schmidt
authors.forename: Clayton
authors.initials: C
authors.lastname: Ehasz
authors.forename: Michael
authors.initials: M
authors.lastname: Epperson
authors.forename: Kimberly
authors.initials: K
authors.lastname: Klas
authors.forename: Justin
authors.initials: J
authors.lastname: Wyatt
authors.forename: Mirko
authors.initials: M
authors.lastname: Hennig
authors.forename: Marcello
authors.initials: M
authors.lastname: Forconi
mesh_terms: D000447:Aldehydes / Q000378:metabolism*; D000588:Amines / Q000737:chemistry; D000818:Animals; D002384:Catalysis; D002417:Cattle; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008823:Micelles; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D000588:Amines; D008823:Micelles; D013501:Surface-Active Agents; D012710:Serum Albumin, Bovine; C116609:3-hydroxybutanal; D005634:Fructose-Bisphosphate Aldolase