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

被引：35

作者：

Haider, Shozeb ^{[2
]}

Joseph, Caleb G. ^{[3
]}

Neidle, Stephen ^{[4
]}

Fierke, Carol A. ^{[5
]}

Fuchter, Matthew J. ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Chem, London SW7 2AZ, England

[2] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland

[3] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA

[4] Univ London, Sch Pharm, Canc Res UK Biomol Struct Grp, London WC1N 1AX, England

[5] Univ Michigan, Dept Biol Chem, Dept Chem, Ann Arbor, MI 48109 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 07期

基金：

美国国家卫生研究院;

关键词：

HDAC; Epigenetic; Chromatin; Histones; Acetylation; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; INHIBITORS; TRANSCRIPTION; SUBSTRATE; DESIGN; HDAC8;

D O I：

10.1016/j.bmcl.2011.01.128

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2129 / 2132

页数：4

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