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Determining histone deacetylase 8 substrates using non‐natural amino acids
Author(s) -
Lopez Jeffrey,
Majmudar Jaimeen,
Martin Brent,
Fierke Carol
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.600.25
Subject(s) - hdac8 , isozyme , acetylation , lysine , biochemistry , histone deacetylase , amino acid , chemistry , enzyme , phenylalanine , histone , bromodomain , gene , histone methyltransferase
The Histone deacetylase family is comprised of 18 isozymes that catalyze the removal of an acetyl group from the ɛ‐position of a lysine. Lysine deacetylation is a post‐translational modification that affects a diverse array of different macromolecules and has been implicated in various types of cancers and neurodegenerative diseases. To elucidate and identify HDAC substrates, we have incorporated the photo reactive, non‐natural amino acid ‐ p‐benzonyl‐4‐phenylalanine (pBpa) ‐ into HDAC8, a structurally well characterized isozyme of this family with a largely unknown substrate pool. Photo cross‐linking will trap both substrates and binding partners of HDAC8 and enhance the understanding of how this enzyme is regulated in vivo . Through this system, we have an initial screen of catalytically active peptides toward HDAC8. In addition, this will validate the approach as a feasible system to prove other HDAC isozymes. Support or Funding Information NIH – RO1G40602 (C.A.F)NIH ‐‐ 1F31GM116619‐01 (J.E.L)