title: Phosphate analogues in the dissection of mechanism.
abstract: Phosphoryl group transfer is central to genetic replication, cellular signalling and many metabolic processes. Understanding the mechanisms of phosphorylation and phosphate ester and anhydride cleavage is key to efforts towards biotechnological and biomedical exploitation of phosphate-handling enzymes. Analogues of phosphate esters and anhydrides are indispensable tools, alongside protein mutagenesis and computational methods, for the dissection of phosphoryl transfer mechanisms. Hydrolysable and non-hydrolysable phosphate analogues have provided insight into the nature and sites of phosphoryl transfer processes. Kinetic isotope effects and crystallography using transition state analogues have painted more detailed pictures of transition states and how enzymes work to stabilise them.
authors.affiliation: Department of Chemistry, Durham University Mountjoy Site, South Road, Durham DH1 3LE, UK; Department of Chemistry, University of Turku, Vatselankatu 2, 20014 Turku, Finland.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Korhonen
authors.affiliation: Department of Chemistry, Durham University Mountjoy Site, South Road, Durham DH1 3LE, UK.
authors.forename: Louis P
authors.initials: LP
authors.lastname: Conway
authors.affiliation: Department of Chemistry, Durham University Mountjoy Site, South Road, Durham DH1 3LE, UK. Electronic address: d.r.w.hodgson@durham.ac.uk.
authors.forename: David R W
authors.initials: DR
authors.lastname: Hodgson
mesh_terms: D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004798:Enzymes; D010710:Phosphates; D012333:RNA, Messenger