Probing enzyme phosphoester interactions by combining mutagenesis and chemical modification of phosphate ester oxygens

James Stivers, Rajesh Nagarajan

Research output: Contribution to journalArticle


This review covers studies that have used sulfur and carbon substitution of phosphate ester oxygens to probe the energetics of protein-ligand interactions, with a deliberate emphasis on enzymatic reactions. Topics discussed include (1) noncovalent interactions with phosphate esters, (2) chemical reactivity of phosphoester, phosphothioester and phosphonoester linkages, (3) free energy analysis, (4) experimental techniques, (5) examples using chemical modification of phosphate esters alone and (6) examples combining chemical modification and mutagenesis.

Original languageEnglish (US)
Pages (from-to)3443-3467
Number of pages25
JournalChemical Reviews
Issue number8
Publication statusPublished - Aug 2006


ASJC Scopus subject areas

  • Chemistry(all)

Cite this