Modulating substrate specificity of histone acetyltransferase with unnatural amino acids

Kinjal Rajesh Mehta, Ching Yao Yang, Jin Montclare

Research output: Contribution to journalArticle

Abstract

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. This journal is

Original languageEnglish (US)
Pages (from-to)3050-3055
Number of pages6
JournalMolecular BioSystems
Volume7
Issue number11
DOIs
StatePublished - Nov 1 2011

Fingerprint

Histone Acetyltransferases
Substrate Specificity
Amino Acids
Histones
p-Fluorophenylalanine
Proteins
Fluorine
Phenylalanine
p300-CBP-associated factor
Enzymes

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Modulating substrate specificity of histone acetyltransferase with unnatural amino acids. / Mehta, Kinjal Rajesh; Yang, Ching Yao; Montclare, Jin.

In: Molecular BioSystems, Vol. 7, No. 11, 01.11.2011, p. 3050-3055.

Research output: Contribution to journalArticle

Mehta, Kinjal Rajesh ; Yang, Ching Yao ; Montclare, Jin. / Modulating substrate specificity of histone acetyltransferase with unnatural amino acids. In: Molecular BioSystems. 2011 ; Vol. 7, No. 11. pp. 3050-3055.
@article{b166e8d3499542078ad451eae25ecef2,
title = "Modulating substrate specificity of histone acetyltransferase with unnatural amino acids",
abstract = "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. This journal is",
author = "Mehta, {Kinjal Rajesh} and Yang, {Ching Yao} and Jin Montclare",
year = "2011",
month = "11",
day = "1",
doi = "10.1039/c1mb05148b",
language = "English (US)",
volume = "7",
pages = "3050--3055",
journal = "Molecular BioSystems",
issn = "1742-206X",
publisher = "Royal Society of Chemistry",
number = "11",

}

TY - JOUR

T1 - Modulating substrate specificity of histone acetyltransferase with unnatural amino acids

AU - Mehta, Kinjal Rajesh

AU - Yang, Ching Yao

AU - Montclare, Jin

PY - 2011/11/1

Y1 - 2011/11/1

N2 - 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. This journal is

AB - 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. This journal is

UR - http://www.scopus.com/inward/record.url?scp=80054044435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054044435&partnerID=8YFLogxK

U2 - 10.1039/c1mb05148b

DO - 10.1039/c1mb05148b

M3 - Article

VL - 7

SP - 3050

EP - 3055

JO - Molecular BioSystems

JF - Molecular BioSystems

SN - 1742-206X

IS - 11

ER -