Metal-Directed Protein Self-Assembly and Construction of Selective Metal Binding Sites in Protein-Protein Interfaces

金属定向蛋白质自组装和蛋白质-蛋白质界面选择性金属结合位点的构建

• 批准号: 0908115
• 负责人: Faik Tezcan
• 金额: $ 36万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0908115&HistoricalAwards=false
• 关键词: Metal; Directed; Protein; Self; Assembly

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor F. Akif Tezcan at the University of California, San Diego to carry out fundamental/basic studies on the self-assembly of supramolecular protein architectures directed by metal coordination. Nature uses Proteins as premier building blocks for sophisticated nanoscale architectures that carry out complex tasks and chemical transformations. Yet, the rational assembly of multi-protein complexes is an unmet challenge, because protein-protein interactions comprise an extensive set of weak, non-covalent bonds that are difficult targets for de novo design. In this research program, the strength, directionality and selectivity of metal-ligand interactions are exploited to control protein-protein interactions, thereby achieving specificity and affinity without requiring extensive and complementary binding surfaces. Such inorganic chemical control of protein-protein interactions is ultimately utilized towards the construction of functional, protein-based bioassemblies and novel metallocenters built within protein-protein interfaces. This trans-disciplinary program provides an effective platform for attracting members of underrepresented groups to research careers, mentoring and recruitment of transfer students who have a particularly hard time to adjust to the rigors of a large research university, and outreach to students in local high schools.The research under this award will pave the way for the future generation of stable, porous protein frameworks with reactive interfacial metal centers, biomaterials whose assembly/disassembly can be controlled by external stimuli, and provide fundamental information regarding the evolution of natural metalloproteins and enzymes.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。这个研究奖在无机，生物无机和有机化学计划支持教授F。Akif Tezcan在加州大学圣地亚哥分校进行金属配位指导的超分子蛋白质结构自组装的基础/基础研究。大自然使用蛋白质作为复杂纳米结构的首要构建块，执行复杂的任务和化学转化。然而，多蛋白质复合物的合理组装是一个未满足的挑战，因为蛋白质-蛋白质相互作用包括一组广泛的弱非共价键，这些键是从头设计的困难目标。在这项研究计划中，利用金属-配体相互作用的强度，方向性和选择性来控制蛋白质-蛋白质相互作用，从而实现特异性和亲和力，而不需要广泛和互补的结合表面。这种蛋白质-蛋白质相互作用的无机化学控制最终被用于构建功能性的、基于蛋白质的生物组装体和构建在蛋白质-蛋白质界面内的新型生物中心。这个跨学科项目提供了一个有效的平台，吸引代表性不足的群体的成员研究职业，指导和招募转学生，他们特别难以适应大型研究型大学的严格要求，并与当地高中的学生联系。该奖项下的研究将为未来一代稳定，具有反应性界面金属中心的多孔蛋白质框架，其组装/拆卸可以由外部刺激控制的生物材料，并提供关于天然金属蛋白质和酶进化的基本信息。