Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT
Mechanism of multiple lysine methylation by the SET domain enzyme Rubisco LSMT
复制标题
DOI：
10.1038/nsb946
复制
发表时间：
2003-07-01
期刊：
影响因子：
--
通讯作者：
Hurley, JH
中科院分区：
文献类型：
--
作者：
Trievel, RC;Flynn, EM;Hurley, JH
SET结构域蛋白甲基转移酶催化甲基基团从辅因子S-腺苷甲硫氨酸（SNAMet）转移到蛋白质底物的特定赖氨酸残基，例如组蛋白H3和H4的N-末端尾部和Rubisco全酶复合物的大亚基。豌豆Rubisco大亚基甲基转移酶（LSMT）与赖氨酸或ε-N-甲基赖氨酸（MeLys）和产物S-腺苷高半胱氨酸（AdoHCy）的三元复合物的晶体结构分别测定为2.65和2.55埃。MeLys的ζ-甲基通过碳-氧氢键与酶结合，在催化中起关键作用。甲基供体和受体在催化过程中以线性几何排列，用于甲基的S（N）2亲核转移。MeLys ε-氨基与Rubisco LSMT和SET 7/9之间氢键的差异解释了为什么Rubisco LSMT产生多重甲基化的Lys，而SET 7/9仅产生MeLys。
SET domain protein methyltransferases catalyze the transfer of methyl groups from the cofactor S-adenosylmethionine (AdoMet) to specific lysine residues of protein substrates, such as the N-terminal tails of histones H3 and H4 and the large subunit of the Rubisco holoenzyme complex. The crystal structures of pea Rubisco large subunit methyltransferase ( LSMT) in ternary complexes with either lysine or epsilon-N-methyllysine (MeLys) and the product S-adenosylhomocysteine (AdoHcy) were determined to resolutions of 2.65 and 2.55 Angstrom, respectively. The zeta-methyl group of MeLys is bound to the enzyme via carbon-oxygen hydrogen bonds that play a key role in catalysis. The methyl donor and acceptor are aligned in a linear geometry for S(N)2 nucleophilic transfer of the methyl group during catalysis. Differences in hydrogen bonding between the MeLys epsilon-amino group and Rubisco LSMT and SET7/9 explain why Rubisco LSMT generates multiply methylated Lys, wheras SET7/9 generates only MeLys.