组蛋白甲基转移酶

✍ dations ◷ 2025-06-27 19:53:12 #组蛋白甲基转移酶
组蛋白甲基转移酶(英语:Histone methyltransferase,简称为HMT)是包括组蛋白-赖氨酸N-甲基转移酶与组蛋白-精氨酸N-甲基转移酶在内的是一大类组蛋白修饰酶类,它们催化将一个、两个或三个甲基转移到组蛋白的赖氨酸或精氨酸残基上。被添加上的甲基基团主要位于组蛋白H3和H4的特定赖氨酸或精氨酸上。赖氨酸特异性组蛋白甲基转移酶类可被细分为含SET结构域的和不含SET结构域的两类。顾名思义,它们之间的区别在于存不存在SET这样一种结构域。人类基因所编码的具有组蛋白甲基转移酶活性的蛋白质包括:影响甲基转移酶活性的结构包括:SET结构域(包括130个氨基酸)、前SET和后SET结构域。前SET区域包括半胱氨酸残基,可形成三角锌簇,紧密结合锌原子并使结构稳定。SET结构域本身包含一个富含β-股的催化核心,从而形成几个β折叠区域。 一般在前SET结构域发现的β-股将形成的β-折叠,它带有SET结构域的β-股,导致SET结构域结构的细微变化。These small changes alter the target residue site specificity for methylation and allow the SET domain methyltransferases to target many different residues. This interplay between the pre-SET domain and the catalytic core is critical for enzyme function.In order for the reaction to proceed, S-Adenosyl methionine (SAM) and the lysine residue of the substrate histone tail must first be bound and properly oriented in the catalytic pocket of the SET domain. Next, a nearby tyrosine residue deprotonates the ε-amino group of the lysine residue. The lysine chain then makes a nucleophilic attack on the methyl group on the sulfur atom of the SAM molecule, transferring the methyl group to the lysine side chain.Instead of SET, non-SET domain-containing histone methyltransferase utilizes the enzyme Dot1. Unlike the SET domain, which targets the lysine tail region of the histone, Dot1 methylates a lysine residue in the globular core of the histone, and is the only enzyme known to do so. A possible homolog of Dot1 was found in archaea which shows the ability to methylate archaeal histone-like protein in recent studies.The N terminal of Dot1 contains the active site. A loop serving as the binding site for SAM links the N-terminal and the C-terminal domains of the Dot1 catalytic domain. The C-terminal is important for the substrate specificity and binding of Dot1 because the region carries a positive charge, allowing for a favorable interaction with the negatively charged backbone of DNA. Due to structural constraints, Dot1 is only able to methylate histone H3.There are two different types of protein arginine methyltransferases (PRMTs) and three types of methylation that can occur at arginine residues on histone tails. The first type of PRMTs (PRMT1, PRMT3, CARM1⧸PRMT4, and Rmt1⧸Hmt1) produce monomethylarginine and asymmetric dimethylarginine. The second type (JBP1⧸PRMT5) produces monomethyl or symmetric dimethylarginine. The differences in the two types of PRMTs arise from restrictions in the arginine binding pocket.The catalytic domain of PRMTs consists of a SAM binding domain and substrate binding domain (about 310 amino acids in total). Each PRMT has a unique N-terminal region and a catalytic core. The arginine residue and SAM must be correctly oriented within the binding pocket. SAM is secured inside the pocket by a hydrophobic interaction between an adenine ring and a phenyl ring of a phenylalanine.A glutamate on a nearby loop interacts with nitrogens on the target arginine residue. This interaction redistributes the positive charge and leads to the deprotonation of one nitrogen group, which can then make a nucleophilic attack on the methyl group of SAM. Differences between the two types of PRMTs determine the next methylation step: either catalyzing the dimethylation of one nitrogen or allowing the symmetric methylation of both groups. However, in both cases the proton stripped from the nitrogen is dispersed through a histidine–aspartate proton relay system and released into the surrounding matrix.Histone methylation plays an important role in epigenetic gene regulation. Methylated histones can either repress or activate transcription as different experimental findings suggest. For example, it is likely that the methylation of lysine 9 on histone H3 (H3K9me3) in the promoter region of genes prevents excessive expression of these genes and, therefore, delays cell cycle transition and/or proliferation. See Histone#Chromatin regulation.Abnormal expression or activity of methylation-regulating enzymes has been noted in some types of human cancers, suggesting associations between histone methylation and malignant transformation of cells or formation of tumors. In recent years, epigenetic modification of the histone proteins, especially the methylation of the histone H3, in cancer development has been an area of emerging research. It is now generally accepted that in addition to genetic aberrations, cancer can be initiated by epigenetic changes in which gene expression is altered without genomic abnormalities. These epigenetic changes include loss or gain of methylations in both DNA and histone proteins.There is not yet compelling evidence that suggests cancers develop purely by abnormalities in histone methylation or its signaling pathways, however they may be a contributing factor. For example, down-regulation of methylation of lysine 9 on histone 3 (H3K9me3) has been observed in several types of human cancer (such as colorectal cancer, ovarian cancer, and lung cancer), which arise from either the deficiency of H3K9 methyltransferases or elevated activity or expression of H3K9 demethylases.组蛋白甲基转移酶可以用作癌症的诊断和预后的生物标志物。 另外,关于组蛋白甲基转移酶在细胞的恶性转化,组织的癌发生和肿瘤发生中的功能和调节仍然存在许多问题。EC 1.1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20/21/22  · 2.1/2/3/4/5/6/7(2.7.10/11-12)/8/9  · 3.1/2/3/4(3.4.21/22/23/24)/5/6/7/8/9/10/11/12/13  ·

相关

  • 鹊鸲鹊鸲(学名:Copsychus saularis),又名猪屎渣、吱渣、信鸟或四喜,属鹟科鹊鸲属。分布于中国南部及南亚、东南亚国家。在印度它是一种观赏鸟,更是孟加拉国的国鸟。鹊鸲雄鸟体长19厘米
  • 图尔战役估计15,000至20,000,其他估计有30,000至80,000。据阿拉伯史料,约400,000多人。估计20,000至25,000,其他估计上限为80,000,一般常见估计为50,000。110012,000图尔战役又称普瓦捷
  • 远视远视(Hypermetropia, Hyperopia)是指平行光线经过眼的屈光介质在视网膜后聚焦的不正常屈光状态。轻度远视的患者因为眼的调节功能大多不会有症状,40岁左右的轻度患者因为调节功
  • 回盲瓣回盲瓣(Ileocecal valve)是分隔大肠和小肠的括约肌。主要功能是避免大肠内的物质回流进回肠。每天约有二升的流体会经过回盲瓣进入大肠。
  • 亚历山大·冯·洪堡弗里德里希·威廉·海因里希·亚历山大·冯·洪堡(德语:Friedrich Wilhelm Heinrich Alexander von Humboldt,1769年9月14日-1859年5月6日),德国自然科学家、自然地理学家,近代气候
  • 米氮平米氮平(英语:Mirtazapine),商品名为乐活忧(港台)/瑞美隆(中国大陆)(Remeron),是一种去甲肾上腺素和特异性5-羟色胺能抗抑郁药 (NaSSA) ,主要用来治疗抑郁症。米氮平也经常被用作抗焦虑
  • 负回授负反馈(英语:negative feedback),是反馈的一种。是指系统的输出会影响系统的输入,在输出变动时,所造成的影响恰和原来变动的趋势相反;反之,就称为正反馈。另一种说法是系统在一个条
  • 神经末梢神经末梢是神经的末端,能感受外来刺激并传递给神经中枢,或把神经中枢的冲动传达给有关组织。神经末梢可以分为感觉神经末梢和运动神经末梢。感觉神经末梢是感觉神经(亦称传入神
  • 亚历山大·瓦尔沙夫斯基亚历山大·瓦尔沙夫斯基(英语:Alexander Varshavsky,1946年11月8日-),俄裔美国生物化学家,加州理工学院教授。通过对酵母和高等生物的细胞培养的遗传学研究,瓦尔沙夫斯基阐明了从事
  • 彼得·诺威尔彼得·诺威尔(英语:Peter C. Nowell,1928年2月8日-),美国癌症研究家、费城染色体发现者之一。1948年在卫斯理大学获学士学位,1952年在宾夕法尼亚大学获硕士学位,1952年成为该校教员