Trievel Raymond C, Beach Bridgette M, Dirk Lynnette M A, Houtz Robert L, Hurley James H
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell. 2002 Oct 4;111(1):91-103. doi: 10.1016/s0092-8674(02)01000-0.
Protein lysine methylation by SET domain enzymes regulates chromatin structure, gene silencing, transcriptional activation, plant metabolism, and other processes. The 2.6 A 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.
由SET结构域酶介导的蛋白质赖氨酸甲基化作用可调控染色质结构、基因沉默、转录激活、植物代谢及其他过程。核酮糖-1,5-二磷酸羧化酶/加氧酶大亚基甲基转移酶与S-腺苷同型半胱氨酸及一个HEPES离子形成的假双底物复合物的分辨率为2.6埃的结构揭示，SET结构域具有全β结构，嵌入在更大的α-螺旋酶折叠结构中。SET结构域的保守区域在由一个孔连接的两个位点结合S-腺苷甲硫氨酸和底物赖氨酸。我们提出，甲基转移是由连接这些位点的狭窄孔道处的一个保守酪氨酸催化的。辅因子通过与底物相对的酶的另一侧的“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。
