Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L

	Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L
	Gowher, H; Liebert, K; Hermann, A; Xu, GL; Jeltsch, A
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2005
卷号	280 期号:14 页码:13341-13348
通讯作者	Jeltsch, A (reprint author), Int Jacobs Univ Bremen, Sch Sci & Engn, Campus Ring 1, D-28759 Bremen, Germany.,a.jeltsch@iu-bremen.de
英文摘要	Dnmt3L has been identified as a stimulator of the catalytic activity of de novo DNA methyltransferases. It is essential in the development of germ cells in mammals. We show here that Dnmt3L stimulates the catalytic activity of the Dnmt3A and Dnmt3B enzymes by directly binding to their respective catalytic domains via its own C-terminal domain. The catalytic activity of Dnmt3A and -3B was stimulated similar to 15-fold, and Dnmt3L directly binds to DNA but not to S-adenosyl-L-methionine (AdoMet). Complex formation between Dnmt3A and Dnmt3L accelerates DNA binding by Dnmt3A 20-fold and lowers its Km for DNA. Interaction of Dnmt3L with Dnmt3A increases the binding of the coenzyme AdoMet to Dnmt3A, and it lowers the Km of Dnmt3A for AdoMet. On the basis of our data we propose a model in which the interaction of Dnmt3A with Dnmt3L induces a conformational change of Dnmt3A that opens the active site of the enzyme and promotes binding of DNA and the AdoMet. We demonstrate that the interaction of Dnmt3A and Dnmt3L is transient, and after DNA binding to Dnmt3A, Dnmt3L dissociates from the complex. Following dissociation of Dnmt3L, Dnmt3A adopts a closed conformation leading to slow rates of DNA release. Therefore, Dnmt3L acts as a substrate exchange factor that accelerates DNA and AdoMet binding to de novo DNA methyltransferases.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	DNA CYTOSINE-5 METHYLTRANSFERASES ; DE-NOVO METHYLATION ; TRANSCRIPTIONAL REPRESSOR ; IMMUNODEFICIENCY SYNDROME ; MAMMALIAN DEVELOPMENT ; ENZYMATIC-PROPERTIES ; HISTONE DEACETYLASE ; IN-VIVO ; BINDING ; GENE
收录类别	SCI
语种	英语
WOS记录号	WOS:000228095500020
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1974]
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	Gowher, H,Liebert, K,Hermann, A,et al. Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2005,280(14):13341-13348.
APA	Gowher, H,Liebert, K,Hermann, A,Xu, GL,&Jeltsch, A.(2005).Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L.JOURNAL OF BIOLOGICAL CHEMISTRY,280(14),13341-13348.
MLA	Gowher, H,et al."Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L".JOURNAL OF BIOLOGICAL CHEMISTRY 280.14(2005):13341-13348.