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Phosphate analogues in the dissection of mechanism

Authors
Journal
Current Opinion in Chemical Biology
1367-5931
Publisher
Elsevier
Volume
21
Identifiers
DOI: 10.1016/j.cbpa.2014.05.001
Disciplines
  • Biology
  • Computer Science
  • Medicine

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.

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