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. |
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