組蛋白乙醯轉移酶
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 | |||||||
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組蛋白乙醯轉移酶MYST1的結構 | |||||||
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識別碼 | |||||||
EC編號 | 2.3.1.48 | ||||||
CAS號 | 9054-51-7 | ||||||
數據庫 | |||||||
IntEnz | IntEnz瀏覽 | ||||||
BRENDA | BRENDA入口 | ||||||
ExPASy | NiceZyme瀏覽 | ||||||
KEGG | KEGG入口 | ||||||
MetaCyc | 代謝路徑 | ||||||
PRIAM | 概述 | ||||||
PDB | RCSB PDB PDBj PDBe PDBsum | ||||||
基因本體 | AmiGO / EGO | ||||||
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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
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