title: Evolutionary drivers of thermoadaptation in enzyme catalysis.
abstract: With early life likely to have existed in a hot environment, enzymes had to cope with an inherent drop in catalytic speed caused by lowered temperature. Here we characterize the molecular mechanisms underlying thermoadaptation of enzyme catalysis in adenylate kinase using ancestral sequence reconstruction spanning 3 billion years of evolution. We show that evolution solved the enzyme's key kinetic obstacle-how to maintain catalytic speed on a cooler Earth-by exploiting transition-state heat capacity. Tracing the evolution of enzyme activity and stability from the hot-start toward modern hyperthermophilic, mesophilic, and psychrophilic organisms illustrates active pressure versus passive drift in evolution on a molecular level, refutes the debated activity/stability trade-off, and suggests that the catalytic speed of adenylate kinase is an evolutionary driver for organismal fitness.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Vy
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Wilson
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Hoemberger
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Stiller
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Agafonov
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Steffen
authors.initials: S
authors.lastname: Kutter
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: English
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Theobald
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, Brandeis University, Waltham, MA 02452, USA. dkern@brandeis.edu.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kern
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D055162:Biocatalysis; D019143:Evolution, Molecular; D006358:Hot Temperature; D007700:Kinetics; D009154:Mutation; D010802:Phylogeny; D000071436:Thermotolerance
chemical_list: D000262:Adenylyl Cyclases