Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity

	Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity
	Zha, MW; Zhong, C; Peng, YJ; Hu, HY; Ding, JP
刊名	JOURNAL OF MOLECULAR BIOLOGY
	2006
卷号	364 期号:5 页码:1021-1033
关键词	nudix domain ADPR ADP-ribose pyrophosphatase NUDT5 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	Human NUDT5 (hNUDT5) is an ADP-ribose pyrophosphatase (ADPRase) belonging to the Nudix hydrolase superfamily. It presumably plays important roles in controlling the intracellular level of ADP-ribose (ADPR) to prevent non-enzymatic ADP-ribosylation by hydrolyzing ADPR to AMP and ribose 5'-phosphate. We report here the crystal structures of hNUDT5 in ago form, in complex with ADPR, and in complex with AMP with bound Mg2+. hNUDT5 forms a homodimer with substantial domain swapping and assumes a structure more similar to Escherichia coli ADPRase ORF209 than human ADPRase NUDT9. The adenine moiety of the substrates is specifically recognized by the enzyme via hydrogenbonding interactions between N1 and N6 of the base and Glu47 of one subunit, and between N7 of the base and Arg51 of the other subunit, providing the molecular basis for the high selectivity of hNUDT5 for ADP-sugars over other sugar nucleotides. Structural comparisons with E. coli ADPRase ORF209 and ADPXase ORF186 indicate that the existence of an aromatic residue on loop L8 in ORF186 seems to be positively correlated with its enzymatic activity on AP(n)A, whereas hNUDT5 and ORF209 contain no such residue and thus have low or no activities on APnA. (c) 2006 Elsevier Ltd. All rights reserved.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ADP-RIBOSE PYROPHOSPHATASE ; DIADENOSINE TETRAPHOSPHATE HYDROLASE ; NUDIX HYDROLASE ; HUMAN ERYTHROCYTES ; PROTEINS ; RIBOSYLATION ; MECHANISM ; CLONING ; IDENTIFICATION ; EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000242769200015
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1717]
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	Zha, MW,Zhong, C,Peng, YJ,et al. Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity[J]. JOURNAL OF MOLECULAR BIOLOGY,2006,364(5):1021-1033.
APA	Zha, MW,Zhong, C,Peng, YJ,Hu, HY,&Ding, JP.(2006).Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity.JOURNAL OF MOLECULAR BIOLOGY,364(5),1021-1033.
MLA	Zha, MW,et al."Crystal structures of human NUDT5 reveal insights into the structural basis of the substrate specificity".JOURNAL OF MOLECULAR BIOLOGY 364.5(2006):1021-1033.