Phase II SER-CAT Optimization: Acquisition of a next generation area detector

第二阶段 SER-CAT 优化：购买下一代区域探测器

• 批准号: 7839456
• 负责人: BI-CHENG WANG
• 金额: $ 147.2万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7839456
• 关键词: 5 year old; Area; Back; Capital; Cell physiology; Crystallography; Data; Data Collection; Disease; Event; Extramural Activities; Faculty; Failure; Funding; Funding Applicant; Institution; Knowledge; Laboratories; Lead; Molecular; Nose; Phase; Photons; Proteins; Research; Research Activity; Research Project Grants; Roentgen Rays; Signal Transduction; Source; Speed; Structure; Structure-Activity Relationship; Students; Therapeutic; Time; United States National Institutes of Health; base; detector; drug discovery; improved; insight; member; next generation; programs; protein structure function; research study; structural biology; success; three dimensional structure

DESCRIPTION (provided by applicant): Funds are requested for the purchase of a next generation, high-speed X-ray detector for the Southeast Regional Collaborative Access Team (SER-CAT) Sector 22, Advanced Photon Source, Argonne National Laboratory (www.ser-cat.org), as the Phase II optimization of 22ID. Organized in 1997, SER-CAT has grown to include over 90 research groups from 25 institutions spanning 14 states. The SER-CAT beam lines provide data and structures in support of (1) federally funded and other research activities, (2) industrial drug discovery and (3) preliminary results needed for new proposals. SER-CAT's success is reflected by the fact that its premiere beam line 22ID has become one of the world's most productive facilities for macromolecular crystallography. SER-CAT member institutions view SER-CAT to be critical to their structural biology programs and in attracting (and retaining) the best and brightest faculty and students. The fact that each institution must pay yearly dues (based on their share of capital expense) to maintain the facility and to receive beam time reflects the importance of SER-CAT to their programs. The aims of the proposed acquisition of a next generation, fast detector are: (1) the current detector in use on 22ID is now over five years old and nearing the point where reliability can become an issue. Thus, good management requires that SER-CAT be proactive in assuring its membership access to a reliable large format CCD detector on its premier beam line. (2) The current proposal represents Phase II of our planned optimization of data collection capability at SER-CAT. The proposed detector will maximize the impact of the Phase I microdiffractometer acquisition by improving the signal-to-nose ratio for data from weekly diffracting micro crystals that our members often find difficult to collect data from at SER-CAT. (3) The proposed Rayonix MX325-HS-100T detector (with its 0.097 sec readout) should double or triple the number of experiments that can be carried out per day on 22ID, which in-turn should increase the success of extramural funding (i.e. more projects get beam time producing more results). (4) The proposed detector will allow us to move the current MX300 detector on 22ID to the SER-CAT bending magnet beam line 22BM. This move will significantly increase the range of experiments that can be carried out on 22BM. importantly; the MX300 detector will serve as a needed backup for 22ID with the MAR 225 installed back on 22BM, in the event of 22ID detector failure. SER-CAT currently supports over 80 NIH funded research projects aimed at producing three-dimensional structures of proteins related to understanding protein structure-function relationships and their mechanism of action. These studies will significantly impact our knowledge of cellular processes and provide valuable insights into the molecular basis of disease that will lead to better therapeutics.

描述（由申请人提供）：申请资金用于为东南区域合作访问小组（SER-CAT）第22区高级光子源，阿贡国家实验室（www.ser-cat.org）购买下一代高速X射线探测器，作为22 ID的第二阶段优化。SER-CAT成立于1997年，现已发展到包括来自14个州的25个机构的90多个研究小组。SER-CAT光束线提供数据和结构，以支持（1）联邦资助和其他研究活动，（2）工业药物发现和（3）新提案所需的初步结果。SER-CAT的成功反映在其首台光束线22 ID已成为世界上最具生产力的大分子晶体学设施之一。 SER-CAT成员机构认为SER-CAT对其结构生物学课程至关重要，并吸引（和留住）最优秀和最聪明的教师和学生。事实上，每个机构都必须支付年费（根据他们的资本支出份额），以维持设施和接收光束时间反映了SER-CAT对他们的计划的重要性。 拟议采购下一代快速探测器的目的是：（1）目前在22 ID上使用的探测器已经使用了五年多，接近可靠性可能成为一个问题的程度。因此，良好的管理要求SER-CAT积极主动地确保其成员在其主要光束线上获得可靠的大格式CCD探测器。(2)目前的提议代表了我们计划在SER-CAT进行的数据收集能力优化的第二阶段。提议的探测器将通过提高每周衍射微晶数据的信噪比来最大化第一阶段微衍射仪采集的影响，我们的成员经常发现很难从SER-CAT收集数据。（3）提议的Rayonix MX325-HS-100 T探测器（读数为0.097秒）应该是每天可以在22 ID上进行的实验数量的两倍或三倍，这反过来应该增加校外资助的成功（即更多的项目获得光束时间产生更多的结果）。(4)建议的探测器将允许我们将22 ID上的当前MX300探测器移动到SER-CAT弯曲磁体束线22 BM。这一举措将大大增加22 BM上可以进行的实验范围。重要的是，如果22 ID探测器发生故障，MX300探测器将作为22 ID所需的备份，MAR 225则安装在22 BM上。SER-CAT目前支持80多个NIH资助的研究项目，旨在产生与理解蛋白质结构-功能关系及其作用机制相关的蛋白质三维结构。这些研究将显著影响我们对细胞过程的认识，并为疾病的分子基础提供有价值的见解，从而获得更好的治疗方法。

项目成果

De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX.

• DOI: 10.1021/acs.jmedchem.9b00878
• 发表时间: 2019-06
• 期刊: Journal of medicinal chemistry
• 影响因子: 7.3
• 作者: Joanne Tan;Julie Grouleff;Y. Jitkova;D. Diaz;E. Griffith;Wenjie Shao;Anastasia F. Bogdanchikova;G. Poda;A. Schimmer;Richard E. Lee;A. Yudin

A ubiquitin-like domain is required for stabilizing the N-terminal ATPase module of human SMCHD1.

稳定人 SMCHD1 的 N 端 ATP 酶模块需要类泛素结构域。

• DOI: 10.1038/s42003-019-0499-y
• 发表时间: 2019
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Pedersen,LarsC;Inoue,Kaoru;Kim,Susan;Perera,Lalith;Shaw,NatalieD
• 通讯作者: Shaw,NatalieD

A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits.

• DOI: 10.1016/j.molcel.2020.10.030
• 发表时间: 2020-12-03
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Wilfling F;Lee CW;Erdmann PS;Zheng Y;Sherpa D;Jentsch S;Pfander B;Schulman BA;Baumeister W
• 通讯作者: Baumeister W

Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections.

• DOI: 10.1073/pnas.2122506119
• 发表时间: 2022-05-31
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

A human antibody epitope map of Pfs230D1 derived from analysis of individuals vaccinated with a malaria transmission-blocking vaccine.

• DOI: 10.1016/j.immuni.2023.01.012
• 发表时间: 2023-02
• 期刊: Immunity
• 影响因子: 32.4
• 作者: W. Tang;C. Coelho;K. Miura;Bergeline C. Nguemwo Tentokam;N. Salinas;D. Narum;S. Healy;I. Sagara;C. Long;P. Duffy;N. Tolia