DIMERIZATION AND ACTIVATION MECHANISM OF PKNB, A SERINE/THREONINE KINASE FROM MT
MT丝氨酸/苏氨酸激酶PKNB的二聚化和激活机制
基本信息
- 批准号:7954331
- 负责人:
- 金额:$ 0.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-03-01 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:Active SitesBiochemicalCell ShapeCell divisionComputer Retrieval of Information on Scientific Projects DatabaseDataDevelopmentDimerizationFundingGrantInstitutionMass Spectrum AnalysisMediatingMutationMycobacterium tuberculosisPhosphorylationPhosphotransferasesProcessProtein-Serine-Threonine KinasesResearchResearch PersonnelResolutionResourcesSideSignal TransductionSourceStructureTherapeuticUnited States National Institutes of Healthdimerinterestmonomermutantnovelstructural biologysynchrotron radiation
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Mycobacterium tuberculosis (MTB) contains 11 predicted eukaryotic-like serine/threonine protein kinases (STPKs). Signal transduction mediated by PknB, an MTB STPK, regulates cell shape, and possibly cell division. In this study, we will examine the significance of the highly conserved PknB dimerization interface, which is located on the side opposite the active site. Initial structural determination of a dimerization interface mutant (L33D) showed a monomer which was missing critical catalytic contacts, and mass spectrometry indicated less phosphorylation than wild-type PknB. Additionally, preliminary biochemical data suggests that PknB autophosphorylation is enhanced by dimer formation and that this process is intermolecular. To further characterize the activation mechanism of PknB, we are interested in determining the crystal structures of the inactive kinase using a catalytically dead mutant (D138N) alone, and in combination with the dimer interface mutation. We also hope to obtain higher-quality atomic resolution data for the L33D structures. These studies will further define the regulatory mechanisms of STPKs and aid in the development of novel MTB therapeutics.
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
结核分枝杆菌(MTB)含有11种预测的真核生物样丝氨酸/苏氨酸蛋白激酶(STPKs)。 由PknB(MTB STPK)介导的信号转导调节细胞形状,并且可能调节细胞分裂。 在这项研究中,我们将研究高度保守的PknB二聚化界面的意义,它位于活性位点的对面。 二聚化界面突变体(L33 D)的初始结构测定显示缺少关键催化接触的单体,并且质谱分析表明磷酸化比野生型PknB少。 此外,初步的生物化学数据表明,PknB自身磷酸化增强二聚体的形成,这一过程是分子间的。 为了进一步表征PknB的激活机制,我们感兴趣的是使用单独的催化死亡突变体(D138 N)以及与二聚体界面突变相结合来确定失活激酶的晶体结构。 我们还希望获得L33 D结构的更高质量的原子分辨率数据。 这些研究将进一步确定STPK的调控机制,并有助于开发新型MTB治疗剂。
项目成果
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{{ truncateString('T NOELLE LOMBANA', 18)}}的其他基金
DIMERIZATION AND ACTIVATION MECHANISM OF PKNB, A SERINE/THREONINE KINASE FROM MT
MT丝氨酸/苏氨酸激酶PKNB的二聚化和激活机制
- 批准号:
7721983 - 财政年份:2008
- 资助金额:
$ 0.02万 - 项目类别:
DIMERIZATION AND ACTIVATION MECHANISM OF PKNB, A SERINE/THREONINE KINASE FROM MT
MT丝氨酸/苏氨酸激酶PKNB的二聚化和激活机制
- 批准号:
7598238 - 财政年份:2007
- 资助金额:
$ 0.02万 - 项目类别:
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