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
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8078336
• 关键词: APRIN gene; Active Sites; Binding; Binding Sites; Biochemical; Biochemistry; Biological Assay; Calorimetry; Catalytic Domain; Charge; Collaborations; Complex; Core Protein; Crystallization; Cytidine Deaminase; Cytosine deaminase; DNA; Data; Disease; Docking; Enzymes; Equilibrium; Family; Goals; Grant; Guidelines; HIV; HIV therapy; HIV-1; Homo; Homology Modeling; Human body; Imagery; Infection; Investigation; Ligands; Maps; Mass Spectrum Analysis; Modeling; Molecular; Molecular Models; Mutate; Mutation; Pathway interactions; Peptides; Pharmaceutical Preparations; Pharmacotherapy; Protein Family; Proteins; Resolution; Role; Series; Shapes; Solutions; Specificity; Structure; Substrate Interaction; Surface; Techniques; Testing; Variant; Viral; Viral Physiology; Virus; Virus Diseases; Work; Zinc; acrosome stabilizing factor; analog; crosslink; design; inhibitor/antagonist; interdisciplinary approach; macromolecule; molecular modeling; mutant; novel; prevent; response; scaffold; small molecule; virology

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.

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，特别是在响应HIV-1时。尽管这些重要酶的催化结构域的结构已开始阐明，但其特异性和与其他细胞和病毒大分子的相互作用的细节仍然有待确定。在此提案中，我们使用了晶体学，分子建模，量热法，质谱和病毒研究的组合来表征这些各种APOBEC3的结构域，均在其结构域内内部分子以及与HIV-1 VIF的相互作用的群体内分子。