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	Crystal structures of streptococcus mutans 2 '-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dctp center dot mg2+
	Hou, Hai-Feng1,2; Liang, Yu-He3; Li, Lan-Fen3; Su, Xiao-Dong3; Dong, Yu-Hui1
刊名	Journal of molecular biology
	2008-03-14
卷号	377期号:1页码:220-231
关键词	Crystal structure 2 '-deoxycytidylate deaminase Enzyme complex Allosteric regulation Deoxycytidine-5'-triphosphate
ISSN号	0022-2836
DOI	10.1016/j.jmb.2007.12.064
通讯作者	Dong, yu-hui(dongyh@ihep.ac.cn)
英文摘要	2 '-deoxycytidylate deaminase [or deoxycytidine-5 '-monophosphate (dcmp) deaminase, dcd] catalyzes the deamination of dcmp to deoxyuridine-5 '-monophosphate to provide the main nucleotide substrate for thymidylate synthase, which is important in dna synthesis. the activity of this homohexameric enzyme is allosterically regulated by deoxycytidine-5 '-triphosphate (dctp) as an activator and by deoxythymidine-5 '-triphosphate as an inhibitor. in this article, we report the crystal structures of dcmp deaminase from streptococcus mutans and its complex with dctp and an intermediate analog at resolutions of 3.0 and 1.66 a. the protein forms a hexamer composed of subunits adopting a three-layer alpha /beta/alpha sandwich fold. the positive allosteric regulator dctp mainly binds at the interface between two monomers in a molar ratio of 1:1 and rearranges the neighboring interaction networks. structural comparisons and sequence alignments revealed that dcmp deaminase from streptococcus mutans belongs to the cytidine deaminase superfamily, wherein the proteins exhibit a similar catalytic mechanism. in addition to the two conserved motifs involved in the binding of zn2+, a new conserved motif, (g(43)yng(46)), related to the binding of dctp was also identified. n-terminal arg4, a key residue located between two monomers, binds strongly to the gamma phosphate group of dctp. the regulation signal was transmitted by arg4 from the allosteric site to the active site via modifications in the interactions at the interface where the substrate-binding pocket was involved and the relocations of arg26, his65, tyr120, and arg121 to envelope the active site in order to stabilize substrate binding in the complex. based on the enzyme-regulator complex structure observed in this study, we propose an allosteric mechanism for dcd regulation. (c) 2007 elsevier ltd. all rights reserved.
WOS关键词	T4-PHAGE DEOXYCYTIDYLATE DEAMINASE ; HEPATITIS-B-VIRUS ; CYTIDINE DEAMINASE ; PROTEIN ; CRYSTALLOGRAPHY ; ALIGNMENT ; SEQUENCE ; SUITE
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000254428200017
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2175878
专题	高能物理研究所
通讯作者	Dong, Yu-Hui
作者单位	1.Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Fac, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China 3.Peking Univ, Coll Life Sci, Natl Lab Protein Engn & Plant Genet Engn, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Hou, Hai-Feng,Liang, Yu-He,Li, Lan-Fen,et al. Crystal structures of streptococcus mutans 2 '-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dctp center dot mg2+[J]. Journal of molecular biology,2008,377(1):220-231.
APA	Hou, Hai-Feng,Liang, Yu-He,Li, Lan-Fen,Su, Xiao-Dong,&Dong, Yu-Hui.(2008).Crystal structures of streptococcus mutans 2 '-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dctp center dot mg2+.Journal of molecular biology,377(1),220-231.
MLA	Hou, Hai-Feng,et al."Crystal structures of streptococcus mutans 2 '-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dctp center dot mg2+".Journal of molecular biology 377.1(2008):220-231.

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