NYSGXRC:A Large Scale Center for the PSI

NYSGXRC：PSI 大型中心

• 批准号: 7090570
• 负责人: Stephen Kevin Burley
• 金额: $ 935.39万
• 依托单位: SGX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7090570
• 关键词: biomedical resource; cooperative study; functional /structural genomics; high throughput technology; protein structure

DESCRIPTION (provided by applicant): Structural GenomiX, Inc., Albert Einstein College of Medicine, the Department of Biology at Brookhaven National Laboratory, Columbia University, Sloan Kettering Institute, and the University of California at San Francisco comprise the New York Structural Genomics Research Consortium (NYSGXRC). This U54 application proposes to establish and operate a Large Scale Center for Phase 2 of the Protein Structure Initiative (PSI-2), as specified in RFA-GM-05-001. Together, members of the NYSGXRC will establish and operate a fully-integrated, high-throughput center for the following activities: (i) protein family classification and target selection, (ii) protein expression and solubility testing, (iii) E. coli and baculovirus fermentation, (iv) purification and biophysical characterization, (v) crystallization, (vi) synchrotron X-ray diffraction data collection, (vii) X-ray phase determination via molecular replacement, multi- and single-wavelength anomalous dispersion measurements, and isomorphous replacement, (viii) model building and refinement, (ix) PDB deposition of atomic coordinates and experimental structure factors, (x) comparative protein structure modeling, and (xi) functional annotation and dissemination of results. Targets for this effort will be derive from three sources, including the PSI-2 Centralized Target Selection Committee (ca. 70% of capacity), an NYSGXRC biomedical research program focused on the phosphatase superfamily (ca. 15% of capacity), and targets solicited from the larger scientific community (ca. 15% of capacity). A program of technology development will also be undertaken to both increase efficiency/throughput and accelerate structure determination for challenging, multi-domain eukaryotic proteins. At peak production, the NYSGXRC will be capable of determining 200 or more structures annually at an average cost approaching $50,000-60,000/structrure for proteins that can be expressed in E. coli. The long-term goal of the NYSGRC is to contribute substantially to the 5,000-10,000 structure objective of PSI-2.

描述（由申请人提供）：Structural GenomiX, Inc.、阿尔伯特·爱因斯坦医学院、布鲁克海文国家实验室生物学系、哥伦比亚大学、斯隆·凯特琳研究所和加州大学旧金山分校组成了纽约结构基因组学研究中心财团（NYSGXRC）。该 U54 申请建议按照 RFA-GM-05-001 的规定，为蛋白质结构计划 (PSI-2) 第二阶段建立和运营一个大型中心。 NYSGXRC 成员将共同建立并运营一个完全集成的高通量中心，开展以下活动：(i) 蛋白质家族分类和靶点选择，(ii) 蛋白质表达和溶解度测试，(iii) 大肠杆菌和杆状病毒发酵，(iv) 纯化和生物物理表征，(v) 结晶，(vi) 同步加速器 X 射线衍射数据收集，(vii) 通过分子置换、多波长和单波长确定 X 射线相位异常色散测量和同形替换，(viii) 模型构建和完善，(ix) 原子坐标和实验结构因素的 PDB 沉积，(x) 比较蛋白质结构建模，以及 (xi) 结果的功能注释和传播。这项工作的目标将来自三个来源，包括 PSI-2 集中目标选择委员会（约占能力的 70%）、专注于磷酸酶超家族的 NYSGXRC 生物医学研究计划（约占能力的 15%）和目标从更大的科学界征集（约占容量的 15%）。还将开展一项技术开发计划，以提高效率/通量并加速具有挑战性的多域真核蛋白质的结构测定。在生产高峰期，NYSGXRC 将能够每年确定 200 个或更多结构，平均成本接近 50,000-60,000 美元/结构，用于可在大肠杆菌中表达的蛋白质。 NYSGRC 的长期目标是为 PSI-2 的 5,000-10,000 结构目标做出重大贡献。