课题基金 / 基金详情

STRUCTURES OF RIBONUCLEOTIDE REDUCTASE

STRUCTURES OF RIBONUCLEOTIDE REDUCTASE
核糖核苷酸还原酶的结构
批准号:
8361673
负责人:
Chris G Dealwis
金额:
$4.39万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-04-01 至 2012-03-31

项目摘要

项目成果

Chris G Dealwis的其他基金

相似基金

相关文献

中文摘要
翻译
这个子项目是利用这些资源的众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Ribonucleotide reductase (RR) catalyzes the rate-limiting step of de novo DNA synthesis by reducing NDPs to dNDPs. RR composes of a large catalytic ¿ subunit that houses the catalytic site and two allosteric sites, and a ¿ subunit that houses a free-radical that must be delivered to the catalytic site to initiate catalysis. Recent data show that the active eukaryotic RR1 is hexameric, hence departing from a previously held view of active RR1 dimers. ATP activates RR by inducing RR1 hexamers, while dATP inactivates RR by also inducing RR1 hexamers. One of the key questions that still remain to be answered is how can ATP be an activator while dATP an inhibitor if both effectors induce hexamerization of RR1? Due to the crucial role played by RR in dNTP synthesis, it is targeted for anti-cancer and viral therapy. In the past, we were able to determine the first eukaryotic RR1 structure from yeast (Xu et al., 2006A and 2006B PNAS) and recently the human RR1 (Fairman NSMB, 2010). During this proposal we will solve several structures of hRR1-drug complexes. We have also solved the first dATP-bound RR1 hexamer from yeast, albeit at 6 ¿ resolution. We wish to extend the resolution in order to understand why it is required for dATP to form RR1 hexamers to inactivate RR. In contrast ATP also forms RR1 hexamers and act as an activator of RR. We wish to determine the RR1-ATP hexamer structure to understand the mechanism of RR activation. We have shown that the C-terminus of the small subunit called RR2 can block RR assembly. We will solve structures of RR1 complexed with peptidomimetic libraries that block RR1-RR2 association.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Investigating the structural assembly of RNR multimers
  • 批准号:
    8475488
  • 项目类别:
  • 资助金额:
    $28.35万
  • 财政年份:
    2012
  • 负责人:
    Chris G Dealwis
  • 依托单位:
Investigating the structural assembly of RNR multimers
  • 批准号:
    8909392
  • 项目类别:
  • 资助金额:
    $0.8万
  • 财政年份:
    2012
  • 负责人:
    Chris G Dealwis
  • 依托单位:
Investigating the structural assembly of RNR multimers
  • 批准号:
    8669995
  • 项目类别:
  • 资助金额:
    $29.38万
  • 财政年份:
    2012
  • 负责人:
    Chris G Dealwis
  • 依托单位:
Investigating the structural assembly of RNR multimers
  • 批准号:
    8264407
  • 项目类别:
  • 资助金额:
    $30.78万
  • 财政年份:
    2012
  • 负责人:
    Chris G Dealwis
  • 依托单位:
国内基金
海外基金
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号:
    32170319
  • 项目类别:
    面上项目
  • 资助金额:
    58.00万元
  • 批准年份:
    2021
  • 负责人:
    董春海
  • 依托单位:
帽结合蛋白(cap binding protein)调控乙烯信号转导的分子机制
  • 批准号:
    --
  • 项目类别:
    --
  • 资助金额:
    58万元
  • 批准年份:
    2021
  • 负责人:
    董春海
  • 依托单位:
ID1 (Inhibitor of DNA binding 1) 在口蹄疫病毒感染中作用机制的研究
番茄EIN3-binding F-box蛋白2超表达诱导单性结实和果实成熟异常的机制研究
  • 批准号:
    31372080
  • 项目类别:
    面上项目
  • 资助金额:
    80.0万元
  • 批准年份:
    2013
  • 负责人:
    杨迎伍
  • 依托单位: