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）：要求为东南地区协作访问团队（SER-CAT）22，高级光子源，Argonne国家实验室（www.ser-cat.org）购买下一代的高速X射线探测器（SER-CAT）22阶段的资金。 Ser-Cat成立于1997年，已成长为包括来自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）工业药物发现以及（3）新建议所需的初步结果。 Ser-Cat的成功反映了以下事实：其首映光束线22ID已成为世界上最有生产力的大分子晶体学的设施之一。 Ser-Cat成员机构认为Ser-Cat对其结构生物学计划至关重要，并吸引（并保留）最好，最聪明的教师和学生。每个机构必须每年支付年度会费（基于其资本费用的份额）以维护设施并获得束缚时间，这反映了Ser-Cat对其计划的重要性。 拟议收购下一代的目的是：（1）当前使用22ID的检测器现在已有五年历史，并且接近可靠性可能成为问题的地步。因此，良好的管理要求SER-CAT积极主动确保其成员访问其首要梁线上可靠的大格式CCD检测器。 （2）当前的建议代表了我们计划对SER-CAT的数据收集能力优化的II阶段。提出的检测器将通过提高每周衍射微晶晶体的数据比率来最大程度地提高I期微二流仪采集的影响，而我们的成员通常很难从SER-CAT中收集数据。 （3）所提出的摩擦式MX325-HS-100T检测器（其0.097秒的读数）应加倍或三倍的实验数量，即在22ID上每天进行的实验数量，这应该增加术后资金的成功（即，更多的项目会产生更多的结果，从而产生了更多的结果）。 （4）所提出的检测器将使我们能够在22ID上将当前的MX300检测器移至Ser-Cat弯曲磁铁束线22Bm。这一举动将显着增加可以在22Bm上进行的实验范围。重要的是MX300探测器将作为22ID的必需备份，在22 ID检测器故障的情况下，将在22Bm上安装225次。 SER-CAT目前支持80多个NIH资助的研究项目，旨在产生与了解蛋白质结构功能关系及其作用机理有关的蛋白质的三维结构。这些研究将显着影响我们对细胞过程的了解，并为疾病的分子基础提供宝贵的见解，从而导致更好的治疗疗法。

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