Modulating substrate specificity of histone acetyltransferase with unnatural amino acids

Kinjal Rajesh Mehta, Ching Yao Yang, Jin Kim Montclare

Research output: Contribution to journalArticlepeer-review


Controlling the substrate specificity of enzymes is a major challenge for protein engineers. Here we explore the effects of residue-specific incorporation of ortho-, meta- and para-fluorophenylalanine (oFF, mFF, pFF) on the selectivity of human histone acetyltransferase (HAT) protein, p300/CBP associated factor (PCAF). Varying the position of the fluorine group in the phenylalanine ring confers different effects on the ability of PCAF to acetylate target histone H3 as well as non-histone p53. Surprisingly, pFF-PCAF exhibits an increase in activity for non-histone p53, while mFF-PCAF is selective for histone H3. These results suggest that global incorporation of unnatural amino acids may be used to re-engineer protein specificity.

Original languageEnglish (US)
Pages (from-to)3050-3055
Number of pages6
JournalMolecular BioSystems
Issue number11
StatePublished - Nov 1 2011

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology


Dive into the research topics of 'Modulating substrate specificity of histone acetyltransferase with unnatural amino acids'. Together they form a unique fingerprint.

Cite this