Crystal structures of Streptococcus mutans 2 '-deoxycytidylate deaminase and its complex with substrate analog and allosteric regulator dCTP center dot Mg2+
Hou, HF; Liang, YH; Li, LF; Su, XD; Dong, YH; Dong YH(董宇辉)
刊名JOURNAL OF MOLECULAR BIOLOGY
2008
卷号377期号:1页码:#REF!
关键词crystal structure 2 '-deoxycytidylate deaminase enzyme complex allosteric regulation deoxycytidine-5'-triphosphate
学科分类Biochemistry & Molecular Biology
DOI10.1016/j.jmb.2007.12.064
通讯作者Dong, YH (reprint author), Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Fac, Beijing 100049, Peoples R China.
文章类型Article
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.
类目[WOS]Biochemistry & Molecular Biology
收录类别SCI
WOS记录号WOS:000254428200017
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被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/227012
专题中国科学院高能物理研究所_多学科研究中心_期刊论文
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Hou, HF,Liang, YH,Li, LF,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):#REF!.
APA Hou, HF,Liang, YH,Li, LF,Su, XD,Dong, YH,&董宇辉.(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),#REF!.
MLA Hou, HF,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):#REF!.
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