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Structural Characterization of APOBECS's Atomic interactions

Structural Characterization of APOBECS's Atomic interactions
APOBECS 原子相互作用的结构表征
批准号：
8078336
负责人：
Celia A. Schiffer
金额：
$35.01万
依托单位：
UNIVERSITY OF MINNESOTA
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：
2011-03-01 至 2015-12-31
来源：
https://reporter.nih.gov/project-details/8078336
关键词：
APRIN geneActive SitesBindingBinding SitesBiochemicalBiochemistryBiological AssayCalorimetryCatalytic DomainChargeCollaborationsComplexCore ProteinCrystallizationCytidine DeaminaseCytosine deaminaseDNADataDiseaseDockingEnzymesEquilibriumFamilyGoalsGrantGuidelinesHIVHIV therapyHIV-1HomoHomology ModelingHuman bodyImageryInfectionInvestigationLigandsMapsMass Spectrum AnalysisModelingMolecularMolecular ModelsMutateMutationPathway interactionsPeptidesPharmaceutical PreparationsPharmacotherapyProtein FamilyProteinsResolutionRoleSeriesShapesSolutionsSpecificityStructureSubstrate InteractionSurfaceTechniquesTestingVariantViralViral PhysiologyVirusVirus DiseasesWorkZincacrosome stabilizing factoranalogcrosslinkdesigninhibitor/antagonistinterdisciplinary approachmacromoleculemolecular modelingmutantnovelpreventresponsescaffoldsmall moleculevirology

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中文摘要
翻译
APOBECs(A3G、ASF和可能的A3H)是细胞DNA胞嘧啶脱氨酶，是关键的先天抗病毒药物，特别是在应对HIV-1时。虽然这些重要酶的催化结构域的结构已经开始被阐明，但它们的特异性以及它们与其他细胞和病毒大分子的相互作用的细节仍有待确定。在这项建议中，我们结合结晶学、分子模拟、量热、质谱学和病毒研究来表征这些不同的APOBEC3‘S的结构域，既包括它们结构域内的分子内，也包括它们与HIV-1 VIF相互作用的分子间。
英文摘要
The APOBECS's (A3G, ASF and possibly A3H) are cellular DNA cytosine deaminases that are key innate anti-viral agents, particularly in response to HIV-1. Although the structures of the catalytic domains of these important enzymes are beginning to be elucidated, the details of their specificities and interactions with other cellular and viral macromolecules still remains to be determined. In this proposal we are using a combination of crystallographic, molecular modelling, calorimetry, mass spectrometry and viral studies to characterize the domains of these various APOBEC3's, both intra-moleculariy within their domains and intermoleculariy with their interactions with HIV-1 Vif.
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