Cel Enzymes are the catalysts which allow important chemical reactions to occur on biologically relevant time-scales, and the current understanding of enzymes assumes that each enzyme is specifically tailored for a single reaction. Enzyme promiscuity refers to an enzyme’s ability to catalyze chemical transformations other than its native reactions. The identification of an increasing number of promiscuous enzymes challenges the classical “one enzyme, one activity” dogma.The notion that a single enzyme is capable of efficiently catalyzing a number of different reactions, which proceed through different transition states, is challenging to our current comprehension of enzymes. Although enzyme promiscuity is now a well documented phenomenon, the mechanistic principles underlying this behaviour are not well understood. This proposal aims to study catalytic promiscuity in the alkaline phosphatase superfamily, a class of phosphate and sulphate ester cleaving enzymes which are known to be prone to promiscuous behaviour. Specifically, linear free energy relationships will be used to characterize the bond-making and bond-breaking processes in phosphate/sulfate ester cleavage, and how the enzyme is able to stabilize these events. We will also use site directed mutagenesis and a high throughput selection system based on microdroplets to probe the contributions of individual amino acid residues to the catalytic mechanism and study enzyme evolution. Of particular interest is the question of how one enzyme active site is able to efficiently catalyze several thermodynamically demanding reactions which pass through transition states with vastly different properties under non-enzymatic conditions. In addition to enhancing our basic understanding of enzyme function and evolution, the mechanistic insight gleaned from this study will be instrumental in the directed evolution of enzymes with enhanced activity for specific uses in the biotech industry. Dziedzina nauki natural scienceschemical sciencescatalysisnatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2011-IIF - Marie Curie Action: "International Incoming Fellowships" Zaproszenie do składania wniosków FP7-PEOPLE-2011-IIF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IIF - International Incoming Fellowships (IIF) Koordynator THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE Wkład UE € 200 371,80 Adres TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge Zjednoczone Królestwo Zobacz na mapie Region East of England East Anglia Cambridgeshire CC Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Renata Schaeffer (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
