Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism

	Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism
	Chang, YY; Wu, J; Tong, XJ; Zhou, JQ; Ding, JP
刊名	BIOCHEMICAL JOURNAL
	2011
卷号	433 期号:1 页码:295-302
关键词	crystal structure demethylation H3K36 methylation histone demethylase histone modification substrate specificity
通讯作者	Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn
英文摘要	Saccharomyces cerevesiae Rph1 is a histone demethylase orthologous tc. human JMJD2A (Jumonji-domain-containing protein 2A) that can specifically demethylate tri- and dimethylated Lys(36) of histone H3. c-Rph1, the catalytic core of Rph1, is responsible for the demethylase activity, which is essential for the transcription elongation of some actively transcribed genes. In the present work, we report the crystal structures of c-Rph1 in apo form and in complex with Ni2+ and alpha-KG [2-oxoglutarate (alpha-ketoglutarate)]. The structure of c-Rph1 is composed of a JmjN (Jumonji N) domain, a long beta-hairpin, a mixed structural motif and a JmjC domain. The alpha-KG cofactor forms hydrogen-bonding interactions with the side chains of conserved residues, and the Ni2+ ion at the active site is chelated by conserved residues and the cofactor. Structural comparison of Rph1 with JMJD2A indicates that the substrate-binding cleft of Rph1 is formed with several structural elements of the JmjC domain, the long beta-hairpin and the mixed structural motif; and the methylated Lys(36) of H3 is recognized by several conserved residues of the JmjC domain. In vitro biochemical results show that mutations of the key residues at the catalytic centre and in the substrate-binding cleft abolish the demethylase activity. In vivo growth phenotype analyses also demonstrate that these residues are essential for its functional roles in transcription elongation. Taken together, our structural and biological data provide insights into the molecular basis of the histone demethylase activity and the substrate specificity of Rph1.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	RNA-POLYMERASE-II ; DOMAIN-CONTAINING PROTEINS ; TRANSCRIPTIONAL ELONGATION ; MAXIMUM-LIKELIHOOD ; JMJD2 FAMILY ; METHYLATION ; SET2 ; CEREVISIAE ; H3 ; METHYLTRANSFERASE
收录类别	SCI
语种	英语
WOS记录号	WOS:000290055800005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/919]
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	Chang, YY,Wu, J,Tong, XJ,et al. Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism[J]. BIOCHEMICAL JOURNAL,2011,433(1):295-302.
APA	Chang, YY,Wu, J,Tong, XJ,Zhou, JQ,&Ding, JP.(2011).Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism.BIOCHEMICAL JOURNAL,433(1),295-302.
MLA	Chang, YY,et al."Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism".BIOCHEMICAL JOURNAL 433.1(2011):295-302.