Structure and catalytic mechanism of a SET domain protein methyltransferase
Structure and catalytic mechanism of a SET domain protein methyltransferase
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DOI：
10.1016/s0092-8674(02)01000-0
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发表时间：
2002-10-04
期刊：
影响因子：
64.5
通讯作者：
Hurley, JH
中科院分区：
文献类型：
--
作者：
Trievel, RC;Beach, BM;Hurley, JH
SET结构域酶介导的蛋白质赖氨酸甲基化调节染色质结构、基因沉默、转录激活、植物代谢等过程。Rubisco大亚基甲基转移酶在s -腺苷型同型半胱氨酸和HEPES离子的伪双底配合物中的2.6埃分辨率结构揭示了嵌入在更大的α -螺旋酶折叠中的SET结构域的全β结构。SET结构域的保守区域将s -腺苷甲硫氨酸和底物赖氨酸结合在两个由孔连接的位点上。我们提出甲基转移是由一个保守的Tyr在连接位点的狭窄孔中催化的。辅因子通过与底物相对的酶的“后门”进入，促进高度特异性的蛋白质识别并允许添加多个甲基。
Protein lysine methylation by SET domain enzymes regulates chromatin structure, gene silencing, transcriptional activation, plant metabolism, and other processes. The 2.6 Angstrom resolution structure of Rubisco large subunit methyltransferase in a pseudo-bisubstrate complex with S-adenosylhomocysteine and a HEPES ion reveals an all-beta architecture for the SET domain embedded within a larger alpha-helical enzyme fold. Conserved regions of the SET domain bind S-adenosylmethionine and substrate lysine at two sites connected by a pore. We propose that methyl transfer is catalyzed by a conserved Tyr at a narrow pore connecting the sites. The cofactor enters by a "back door" on the opposite side of the enzyme from substrate, promoting highly specific protein recognition and allowing addition of multiple methyl groups.