Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins

	Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins
	Xu, ST; Zhong, C; Zhang, TL; Ding, JP
刊名	JOURNAL OF MOLECULAR CELL BIOLOGY
	2011
卷号	3 期号:5 页码:293-300
关键词	Smyd2 Smyd proteins SET family histone lysine methyltransferase epigenetics
通讯作者	Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn
英文摘要	The SET- and myeloid-Nervy-DEAF-1 (MYND)-domain containing (Smyd) lysine methyltransferases 1-3 share relatively high sequence similarity but exhibit divergence in the substrate specificity. Here we report the crystal structure of the full-length human Smyd2 in complex with S-adenosyl-L-homocysteine (AdoHcy). Although the Smyd1-3 enzymes are similar in the overall structure, detailed comparisons demonstrate that they differ substantially in the potential substrate-binding site. The binding site of Smyd3 consists mainly of a deep and narrow pocket, while those of Smyd1 and Smyd2 consist of a comparable pocket and a long groove. In addition, Smyd2, which has lysine methyltransferase activity on histone H3-lysine 36, exhibits substantial differences in the wall of the substrate-binding pocket compared with those of Smyd1 and Smyd3 which have activity specifically on histone H3-lysine 4. The differences in the substrate-binding site might account for the observed divergence in the specificity and methylation state of the substrates. Further modeling study of Smyd2 in complex with a p53 peptide indicates that mono-methylation of p53-Lys(372) might result in steric conflict of the methyl group with the surrounding residues of Smyd2, providing a structural explanation for the inhibitory effect of the SET7/9-mediated mono-methylation of p53-Lys(372) on the Smyd2-mediated methylation of p53-Lys(370).
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	HISTONE DEACETYLASE COMPLEX ; SET DOMAIN ; CATALYTIC MECHANISM ; CRYSTAL-STRUCTURE ; CANCER-CELLS ; P53 ACTIVITY ; ACTIVE-SITE ; METHYLATION ; H3 ; ENCODES
收录类别	SCI
语种	英语
WOS记录号	WOS:000296292900006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/797]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xu, ST,Zhong, C,Zhang, TL,et al. Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2011,3(5):293-300.
APA	Xu, ST,Zhong, C,Zhang, TL,&Ding, JP.(2011).Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins.JOURNAL OF MOLECULAR CELL BIOLOGY,3(5),293-300.
MLA	Xu, ST,et al."Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins".JOURNAL OF MOLECULAR CELL BIOLOGY 3.5(2011):293-300.