NYSGXRC:A Large Scale Center for the PSI

NYSGXRC：PSI 大型中心

• 批准号: 7624432
• 负责人: Stephen Kevin Burley
• 金额: $ 17万
• 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 2008-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7624432
• 关键词: Amino Acid Sequence; Baculoviruses; Biology; Biomedical Research; California; Classification; Communities; Crystallization; Data Collection; Deposition; Escherichia coli; Fermentation; Future; Goals; Institutes; Laboratories; Measurement; Medicine; Mission; Modeling; Molecular; New York; Peptide Sequence Determination; Phase; Phosphoric Monoester Hydrolases; Production; Protein Family; Protein Structure Initiative; Proteins; Research; Roentgen Rays; San Francisco; Solubility; Source; Specific qualifier value; Structural Models; Structure; Synchrotrons; Testing; Universities; Vision; X ray diffraction analysis; X-Ray Crystallography; X-Ray Diffraction; college; comparative; cost; member; programs; protein expression; protein structure; structural biology; structural genomics; technology development

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.

Structural GenomiX, Inc.、阿尔伯特·爱因斯坦医学院、布鲁克海文生物学系 国家实验室、哥伦比亚大学、斯隆凯特琳研究所和加州大学圣何塞分校 Francisco 是纽约结构基因组学研究联盟 (NYSGXRC) 的组成部分。 该 U54 申请提议为该蛋白质的第二阶段建立并运营一个大型中心 结构倡议 (PSI-2)，如 RFA-GM-05-001 中指定。 NYSGXRC 的成员将共同努力 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标选择，(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) 通过分子置换进行 X 射线相位测定， 多波长和单波长反常色散测量以及同构替换， (viii) 模型构建和细化，(ix) 原子坐标和实验结构的 PDB 沉积 因素，(x) 比较蛋白质结构建模，以及 (xi) 功能注释和传播 结果。这项工作的目标将来自三个来源，包括 PSI-2 集中目标 遴选委员会（约占容量的 70%），NYSGXRC 生物医学研究项目，重点关注 磷酸酶超家族（约容量的 15%），以及从更大的科学界征求的目标（约 15%）。 容量的 15%）。还将实施一项技术开发计划，以提高 效率/通量并加速具有挑战性的多域真核生物的结构测定 蛋白质。在生产高峰期，NYSGXRC 每年将能够确定 200 个或更多结构 对于可在大肠杆菌中表达的蛋白质，平均成本接近 50,000-60,000 美元/结构。这 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。