組蛋白乙醯轉移酶
組蛋白乙醯轉移酶 | |||||||
---|---|---|---|---|---|---|---|
組蛋白乙醯轉移酶MYST1的結構 | |||||||
| |||||||
识别码 | |||||||
EC編號 | 2.3.1.48 | ||||||
CAS号 | 9054-51-7 | ||||||
数据库 | |||||||
IntEnz | IntEnz浏览 | ||||||
BRENDA | BRENDA入口 | ||||||
ExPASy | NiceZyme浏览 | ||||||
KEGG | KEGG入口 | ||||||
MetaCyc | 代谢路径 | ||||||
PRIAM | 概述 | ||||||
PDB | RCSB PDB PDBj PDBe PDBsum | ||||||
基因本体 | AmiGO / EGO | ||||||
|
組蛋白乙醯轉移酶(Histone acetyltransferase,簡稱HAT)是真核生物細胞中將組蛋白乙醯化的酵素,此類酵素將乙醯輔酶A上的乙醯基轉移至組蛋白N端尾的離氨酸上,組蛋白乙醯化可降低其正電荷,使染色體的結構變疏鬆,促進其他蛋白(如具有布羅莫結構域的轉錄因子)與染色體結合,促進基因的轉錄[1]。
組蛋白乙醯轉移酶可依在細胞中的位置分為A型與B型兩大類[2],其中大多數為前者,位於細胞核中,可將染色體(核小體)上的組蛋白乙醯化以促進基因表現[3];後者則位於細胞質中,種類很少,代表者如HAT1(但較新的研究結果認為HAT1可能也存在細胞核中,甚至可能比細胞質的部分多[4]),可將新轉譯產生、尚未組裝成核小體的組蛋白乙醯化,這些組蛋白進入細胞核組裝成核小體後,在細胞質中加上的乙醯基一般會被組蛋白脫乙醯酶移除[5]。組蛋白乙醯轉移酶還可依序列分為GNAT(Gcn5關聯N-乙醯轉移酶;Gcn5-related N-acetyltransferases)、MYST、p300/CBP等基因家族,此外核受體輔活化子[6]、Rtt109[7]、TFIIIC和CLOCK等蛋白也都有組蛋白乙醯轉移酶的功能[8]。GNAT家族包括Gcn5、HAT1、ELP3、ATF2等,皆具有布羅莫結構域,可與已被乙醯化的組蛋白結合[2];MYST家族包括MOZ、Ybf2、Sas2、Tip60(得名自此四種蛋白名稱的縮寫)、KAT8、KAT6B、KAT7等,其中許多具有鋅指與克羅莫結構域[9]。
組蛋白乙醯化的反應機理因轉移酶的種類不同而異,GNAT家族的轉移酶會同時與乙醯輔酶A和組蛋白結合,形成三元複合體[7],MYST家族的轉移酶則是使用乒乓機制(Ping–pong mechanisms),先得到乙醯基再將其轉移到組蛋白上[10]。Gcn5與Rtt109等轉移酶需其他蛋白的輔助才能將組蛋白乙醯化[6][7],有些需與其他蛋白組成複合體以提升組蛋白乙醯化的效率,如SAGA複合體與NuA4複合體[6][11]。許多疾病與組蛋白乙醯轉移酶的調控異常有關[12][13]。
參考文獻
- ^ Sanchez R, Zhou MM. The role of human bromodomains in chromatin biology and gene transcription. Current Opinion in Drug Discovery & Development. September 2009, 12 (5): 659–65. PMC 2921942 . PMID 19736624.
- ^ 2.0 2.1 Lee KK, Workman JL. Histone acetyltransferase complexes: one size doesn't fit all. Nature Reviews. Molecular Cell Biology. April 2007, 8 (4): 284–95. PMID 17380162. doi:10.1038/nrm2145.
- ^ Weaver R. Molecular Biology. McGraw-Hill. 2007. ISBN 978-0073319940.
- ^ Dutnall RN, Tafrov ST, Sternglanz R, Ramakrishnan V. Structure of the histone acetyltransferase Hat1: a paradigm for the GCN5-related N-acetyltransferase superfamily.. Cell. 1998, 94 (4): 427–38. PMID 9727486. doi:10.1016/s0092-8674(00)81584-6.
- ^ Parthun MR. Hat1: the emerging cellular roles of a type B histone acetyltransferase.. Oncogene. 2007, 26 (37): 5319–28. PMID 17694075. doi:10.1038/sj.onc.1210602.
- ^ 6.0 6.1 6.2 Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiology and Molecular Biology Reviews. June 2000, 64 (2): 435–59. PMC 98999 . PMID 10839822. doi:10.1128/MMBR.64.2.435-459.2000.
- ^ 7.0 7.1 7.2 Yuan H, Marmorstein R. Histone acetyltransferases: Rising ancient counterparts to protein kinases. Biopolymers. February 2013, 99 (2): 98–111. PMC 4017165 . PMID 23175385. doi:10.1002/bip.22128.
- ^ Doi M, Hirayama J, Sassone-Corsi P. Circadian regulator CLOCK is a histone acetyltransferase. Cell. May 2006, 125 (3): 497–508. PMID 16678094. doi:10.1016/j.cell.2006.03.033.
- ^ Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annual Review of Biochemistry. 2001, 70: 81–120. PMID 11395403. doi:10.1146/annurev.biochem.70.1.81.
- ^ Berndsen CE, Albaugh BN, Tan S, Denu JM. Catalytic mechanism of a MYST family histone acetyltransferase. Biochemistry. January 2007, 46 (3): 623–9. PMC 2752042 . PMID 17223684. doi:10.1021/bi602513x.
- ^ Kimura A, Matsubara K, Horikoshi M. A decade of histone acetylation: marking eukaryotic chromosomes with specific codes. Journal of Biochemistry. December 2005, 138 (6): 647–62. PMID 16428293. doi:10.1093/jb/mvi184.
- ^ Cvetanovic M, Kular RK, Opal P. LANP mediates neuritic pathology in Spinocerebellar ataxia type 1. Neurobiol. Dis. December 2012, 48 (3): 526–32. PMC 3987943 . PMID 22884877. doi:10.1016/j.nbd.2012.07.024.
- ^ Klein G, Vande Woude GF. Advances in Cancer Research, Volume 86. Boston: Academic Press. 2002. ISBN 978-0-12-006686-5.