Structure and function relationships regulating SAMHD1's dual enzymatic activities
Structure and function relationships regulating SAMHD1's dual enzymatic activities
批准号:
8992152
负责人:
jinwoo ahn
金额:
$28.53万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-07-01 至 2020-06-30
关键词:
Acquired Immunodeficiency SyndromeAffectAllosteric SiteAntiviral AgentsAspartateAutoimmune DiseasesBindingBiochemicalBiologicalBiological AssayCD4 Positive T LymphocytesCalorimetryCatalysisCatalytic DomainCellsCerebrovascular DisordersChronic Lymphocytic LeukemiaDNA VirusesDataEnzyme KineticsEnzymesEquilibriumFoundationsGoalsGuanineGuanosine TriphosphateHIVHIV InfectionsHIV-1Hereditary DiseaseHistidineImmuneInfectionLengthLigand BindingLinkMolecularMutagenesisMutationMyeloid CellsN-terminalNatural ImmunityNucleic Acid BindingNucleotidesPlayProteinsPublishingRegulationRetroviridaeReverse TranscriptionRoentgen RaysRoleSAM DomainSiteStrokeStructureStructure-Activity RelationshipSubstrate SpecificitySurface Plasmon ResonanceSyndromeTitrationsViralVirus DiseasesWorkX-Ray Crystallographyadaptive immunitybaseblocking factordeoxyribonucleoside triphosphatedesignfightinginsightleukemiamutantnovel therapeutic interventionnucleasenucleoside triphosphatepublic health relevancetherapeutic development
中文摘要
英文摘要
DESCRIPTION (provided by applicant): SAMHD1 is a deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase. It is a host cell restriction factor that plays critical roles in the defense against human immunodeficiency virus 1 (HIV-1) infection. SAMHD1 lowers the cellular concentrations of dNTP such that effective reverse transcription is prohibited. Interestingly, SAMHD1 also possesses nuclease activity, shown to be essential for its HIV-1 restriction. Understanding the molecular and structural basis of these two important biological activities and their regulation will provide important insight into mechanisms of HIV restriction. To this end, we
propose the following Aims: In Aim 1, we will determine the structural basis and molecular mechanisms of SAMHD1 dNTPase activity by nucleoside triphosphates. In Aim 2, the structure-function relationship of the intra- and inter- domain interactions will be investigated. In Aim 3, e will characterize the nuclease activity of SAMHD1 and its structural determinants. Results from this work will provide avenues for designing new therapeutic approaches to fight AIDS.
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Structure and function relationships regulating SAMHD1's dual enzymatic activities
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批准号:9100863
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项目类别:
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资助金额:$28.49万
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财政年份:2015
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负责人:jinwoo ahn
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依托单位:
Structure and function relationships regulating SAMHD1's dual enzymatic activities
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批准号:9313914
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项目类别:
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资助金额:$28.46万
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财政年份:2015
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负责人:jinwoo ahn
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依托单位:
Project 6: Vpr subversion of DNA repair
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资助金额:$43.21万
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财政年份:2007
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负责人:jinwoo ahn
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依托单位:
Protein Production and Biochemical Characterization Core
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批准号:9977942
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项目类别:
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资助金额:$20.81万
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财政年份:2007
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负责人:jinwoo ahn
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依托单位:
Core C
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批准号:7507571
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项目类别:
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资助金额:$63.89万
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财政年份:2007
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负责人:jinwoo ahn
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依托单位:
Protein Core
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项目类别:
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资助金额:$41.52万
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财政年份:--
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依托单位:
Core C
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资助金额:$82.34万
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依托单位:
Protein Core
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资助金额:$45.7万
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依托单位:
Protein Core
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批准号:8546399
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项目类别:
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资助金额:$45.98万
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财政年份:--
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依托单位:
Project 6: Vpr subversion of DNA repair
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批准号:9407944
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资助金额:$47.12万
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负责人:jinwoo ahn
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依托单位:
Project 6: Vpr subversion of DNA repair
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资助金额:$43.21万
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财政年份:--
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Core C
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资助金额:$77.21万
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财政年份:--
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依托单位:
Core C
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资助金额:$78.63万
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财政年份:--
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Protein Production and Biochemical Characterization Core
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资助金额:$20.81万
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财政年份:--
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负责人:jinwoo ahn
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依托单位:
Protein Core
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批准号:9129688
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项目类别:
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资助金额:$41.52万
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财政年份:--
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负责人:jinwoo ahn
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依托单位:
Core C
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批准号:7671241
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项目类别:
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资助金额:$60.49万
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财政年份:--
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负责人:jinwoo ahn
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依托单位:
Protein Core
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批准号:8727034
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项目类别:
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资助金额:$41.52万
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财政年份:--
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负责人:jinwoo ahn
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依托单位:
海外基金