On the function of the internal cavity of histone deacetylase protein 8: R37 is a crucial residue for catalysis

Shozeb Haider, C.G. Joseph, S. Neidle, C.A. Fierke, M.J. Fuchter

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Biochemical studies reveal that a conserved arginine residue (R37) at the centre of the 14 angstrom internal cavity of histone deacetylase (HDAC) 8 is important for catalysis and acetate affinity. Computational studies indicate that R37 forms multiple hydrogen bonding interactions with the backbone carbonyl oxygen atoms of two conserved glycine residues, G303 and G305, resulting in a 'closed' form of the channel. One possible rationale for these data is that water or product (acetate) transit through the catalytically crucial internal channel of HDAC8 is regulated by a gating interaction between G139 and G303 tethered in position by the conserved R37. (C) 2011 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)2129-2132
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume21
Issue number7
DOIs
Publication statusPublished - 01 Apr 2011

ASJC Scopus subject areas

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

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