Macromolecular Crystallographic HighFlux Home Lab X-ray Diffraction System

高分子晶体高通量家庭实验室 X 射线衍射系统

• 批准号: 8247330
• 负责人: Celia A. Schiffer
• 金额: $ 53.1万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247330
• 关键词: Biomedical Research; Crystallography; Drug Design; Funding; Grant; Home environment; Image; Massachusetts; Molecular Structure; Play; Research; Research Personnel; Research Support; Role; Screening procedure; Synchrotrons; System; Training; United States National Institutes of Health; Universities; X ray diffraction analysis; X-Ray Diffraction; data acquisition; detector; graduate student; instrumentation; medical schools; programs

DESCRIPTION (provided by applicant): Macromolecular crystallography plays a central role in biomedical research. At the University of Massachusetts Medical School, crystallographic analysis supports the research of more than 10 investigators. This instrumentation is used in the research that is supported by 13 NIH grants and trains more than 25 graduate students. Our current instrumentation can no longer be depended upon. Even when properly functioning the current instrumentation is incapable of serving the cutting-edge research programs many of the investigators require. A Shared Instrumentation Grant will allow us to purchase a new diffraction system and numerous programs will no longer be limited by an outdated machine. Specifically, we are requesting funds for a Rigaku HighFlux HomeLab x-ray diffraction system with an R-AXIS IV++ image plate detector. For many of our projects this new system will permit data acquisition that is sufficient to answer essential questions in macromolecular structure and drug design. For other research programs, the new system will allow local screening of crystals making synchrotron trips much more efficient. Thus the acquisition of this state-of-the-art crystallographic system will propel our research programs far beyond what we can currently achieve. PUBLIC HEALTH RELEVANCE: Modern medicine requires an understanding of the detailed structures of biological molecules. In this proposal we request funds for an x-ray diffraction system, which will allow us to determine such key biological structures in atomic detail. These details will be used in drug design and in understanding the molecular mechanisms of many human diseases.

描述(申请人提供)：大分子结晶学在生物医学研究中起着核心作用。在马萨诸塞大学医学院，结晶学分析支持10多名研究人员的研究。这项研究得到了美国国立卫生研究院13项拨款的支持，并培训了超过25名研究生。我们目前的仪器不能再依赖了。即使在正常运行的情况下，目前的仪器也不能服务于许多研究人员所需的尖端研究项目。共享仪器拨款将允许我们购买新的衍射系统，许多程序将不再受到过时机器的限制。具体地说，我们正在为Rigaku High Flux HomeLab X射线衍射系统申请资金，该系统带有R轴IV++图像板探测器。对于我们的许多项目，这一新系统将允许获取足以回答大分子结构和药物设计中的基本问题的数据。对于其他研究项目，新系统将允许对晶体进行本地筛选，从而使同步加速器旅行更加高效。因此，收购这一最先进的晶体系统将推动我们的研究计划远远超出我们目前所能实现的目标。 公共卫生相关性：现代医学要求了解生物分子的详细结构。在这项提案中，我们要求为X射线衍射系统提供资金，这将使我们能够确定原子细节的关键生物结构。这些细节将用于药物设计和了解许多人类疾病的分子机制。

项目成果

HIV-1 Protease Inhibitors Incorporating Stereochemically Defined P2' Ligands to Optimize Hydrogen Bonding in the Substrate Envelope.

• DOI: 10.1021/acs.jmedchem.9b00838
• 发表时间: 2019-08
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: L. Rusere;G. J. Lockbaum;Sook-Kyung Lee;M. Henes;K. Kosovrasti;E. Spielvogel;E. Nalivaika;R. Swanstrom

Optimizing the refinement of merohedrally twinned P61 HIV-1 protease-inhibitor cocrystal structures.

优化细化单面孪晶 P61 HIV-1 蛋白酶抑制剂共晶结构。

• DOI: 10.1107/s2059798320001989
• 发表时间: 2020
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Lockbaum,GordonJ;Leidner,Florian;Royer,WilliamE;KurtYilmaz,Nese;Schiffer,CeliaA
• 通讯作者: Schiffer,CeliaA

NAD(H) phosphates mediate tetramer assembly of human C-terminal binding protein (CtBP).

• DOI: 10.1016/j.jbc.2021.100351
• 发表时间: 2021-01
• 期刊: The Journal of biological chemistry
• 作者: Nichols JC;Schiffer CA;Royer WE Jr
• 通讯作者: Royer WE Jr

HIV-1 protease-substrate coevolution in nelfinavir resistance.

奈非那韦耐药中的 HIV-1 蛋白酶-底物协同进化。

• DOI: 10.1128/jvi.00266-14
• 发表时间: 2014
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Kolli,Madhavi;Ozen,Ayşegül;Kurt-Yilmaz,Nese;Schiffer,CeliaA
• 通讯作者: Schiffer,CeliaA