组织蛋白甲基转移酶

✍ dations ◷ 2025-09-02 09:51:56 #组织蛋白甲基转移酶
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

  • 足细胞血液流动在入球小动脉(9)上端,及出球小动脉(11)下端。血液流过肾小球的毛细血管(10),它是通过压力过滤。足细胞(3a及3b,绿色)环绕在毛细管上。血液通滤过"裂隙膈膜"(或滤过裂隙
  • 生物气体生物气体(英语:Biogas,亦称生化气体或生质气体),泛指包括粪肥、污水、都市固体废物及其他生物可降解的有机物质,在缺氧的环境下,经发酵或者无氧消化过程所产生的气体,这些气体主要包
  • 哈里·穆里施哈里·库特·维克托·穆里施(Harry Kurt Victor Mulisch,1927年7月29日-2010年10月30日),荷兰作家,出版超过 30 部小说、戏剧、随笔、诗集与哲学反思。与赫拉德·雷夫(Gerard Reve)
  • 威斯特敏斯特坐标:51°29′58″N 0°07′39″W / 51.49944°N 0.12750°W / 51.49944; -0.12750威斯敏斯特圣彼得协同教堂(The Collegiate Church of St Peter at Westminster),通称威斯敏斯
  • 启始客户启始客户(英语:Launch Customer),或称为“起动客户”、“首批客户”、“启动客户”等,是航空界用来特指先订购并接收某一新机型飞机的客户。通常启始客户会获得飞机制造商一定程
  • 皮节皮节是指各条脊神经(英语:Spinal nerve)在皮肤表面的神经支配范围分布。在人类身上,总计有八对颈神经,其中第一对颈神经不具有任何皮节分布、十二对胸神经、五对腰神经、五对荐神
  • 台湾社会学会台湾社会学会(台湾社会学会,英语:Taiwanese Sociological Association)是台湾的社会学学术组织。成立于1930年成立于中国上海,前身为“中国社会学社”,系由孙本文、许仕廉等学者倡
  • 有分心有分(梵语:bhavānga,巴利语:bhavaṅga),佛教阿毘达摩术语,心识的一种形态,是生命存在的基本要素。由赤铜鍱部提出,现仍传承于巴利佛教中。巴利佛教的有分识学说,主要祖述于《发趣论》
  • 藜亚科详见内文藜亚科(学名:Chenopodioideae)是石竹目苋科的亚科,有大约100属、1400多种植物,单单在中国大陆就已有有39属170种,在华北和西北生长。藜科植物都是草本或灌木;很少是小乔木
  • 教名主保圣人,是守护圣者的意思,是部分基督教宗派对圣人或天使使用的特定称呼之一,通常用于教会所期望保护的某人(例如新受洗的基督徒)、某团体或特项活动。当教会宣布某一圣人是主保