Positional effects of monofluorinated phenylalanines on histone acetyltransferase stability and activity

Natalya Voloshchuk; Anita Y. Zhu; David Snydacker; Jin Kim Montclare

doi:10.1016/j.bmcl.2009.07.093

Positional effects of monofluorinated phenylalanines on histone acetyltransferase stability and activity

Natalya Voloshchuk, Anita Y. Zhu, David Snydacker, Jin Kim Montclare

Chemical and Biomolecular Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

To explore the impact of global incorporation of fluorinated aromatic amino acids on protein function, we investigated the effects of three monofluorinated phenylalanine analogs para-fluorophenylalanine (pFF), meta-fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) on the stability and enzymatic activity of the histone acetyltransferase (HAT), tGCN5. We selected this set of fluorinated amino acids because they bear the same size and overall polarity but alter in side chain shape and dipole direction. Our experiments showed that among three fluorinated amino acids, the global incorporation of pFF affords the smallest perturbation to the structure and function of tGCN5.

Original language	English (US)
Pages (from-to)	5449-5451
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2009.07.093
State	Published - Sep 15 2009

Keywords

Activity
Fluorinated amino acids
Histone acetyltransferase
Protein design
Stability

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2009.07.093

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title = "Positional effects of monofluorinated phenylalanines on histone acetyltransferase stability and activity",

abstract = "To explore the impact of global incorporation of fluorinated aromatic amino acids on protein function, we investigated the effects of three monofluorinated phenylalanine analogs para-fluorophenylalanine (pFF), meta-fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) on the stability and enzymatic activity of the histone acetyltransferase (HAT), tGCN5. We selected this set of fluorinated amino acids because they bear the same size and overall polarity but alter in side chain shape and dipole direction. Our experiments showed that among three fluorinated amino acids, the global incorporation of pFF affords the smallest perturbation to the structure and function of tGCN5.",

keywords = "Activity, Fluorinated amino acids, Histone acetyltransferase, Protein design, Stability",

author = "Natalya Voloshchuk and Zhu, {Anita Y.} and David Snydacker and Montclare, {Jin Kim}",

note = "Funding Information: This work was supported by start up funds, the Othmer Institute for Interdisciplinary Studies, ACS Division of Fluorine Chemistry, the Wechsler Award for Excellence (J.K.M.) and AFOSR. ",

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AU - Zhu, Anita Y.

AU - Snydacker, David

AU - Montclare, Jin Kim

N1 - Funding Information: This work was supported by start up funds, the Othmer Institute for Interdisciplinary Studies, ACS Division of Fluorine Chemistry, the Wechsler Award for Excellence (J.K.M.) and AFOSR.

PY - 2009/9/15

Y1 - 2009/9/15

N2 - To explore the impact of global incorporation of fluorinated aromatic amino acids on protein function, we investigated the effects of three monofluorinated phenylalanine analogs para-fluorophenylalanine (pFF), meta-fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) on the stability and enzymatic activity of the histone acetyltransferase (HAT), tGCN5. We selected this set of fluorinated amino acids because they bear the same size and overall polarity but alter in side chain shape and dipole direction. Our experiments showed that among three fluorinated amino acids, the global incorporation of pFF affords the smallest perturbation to the structure and function of tGCN5.

AB - To explore the impact of global incorporation of fluorinated aromatic amino acids on protein function, we investigated the effects of three monofluorinated phenylalanine analogs para-fluorophenylalanine (pFF), meta-fluorophenylalanine (mFF), and ortho-fluorophenylalanine (oFF) on the stability and enzymatic activity of the histone acetyltransferase (HAT), tGCN5. We selected this set of fluorinated amino acids because they bear the same size and overall polarity but alter in side chain shape and dipole direction. Our experiments showed that among three fluorinated amino acids, the global incorporation of pFF affords the smallest perturbation to the structure and function of tGCN5.

KW - Activity

KW - Fluorinated amino acids

KW - Histone acetyltransferase

KW - Protein design

KW - Stability

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Positional effects of monofluorinated phenylalanines on histone acetyltransferase stability and activity

Abstract

Keywords

ASJC Scopus subject areas

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