Structure-based Discovery of Critical Vulnerabilities of Mycobacteria

基于结构的分枝杆菌关键漏洞发现

基本信息

  • 批准号:
    10456888
  • 负责人:
  • 金额:
    $ 238.76万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-09-01 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

Project Summary – Overall The TB Structural Genomics Consortium (TBSGC) is a collaborative research group that has studied TB’s causative organism, Mycobacterium tuberculosis (Mtb), for the past 15 years. Over the years we have focused our goals to concentrate on proteins that are drug targets for novel antibiotics, and proteins whose structure might contribute to our knowledge of vulnerabilities in Mtb. We also supplemented our structural work with both chemistry and genetics to validate our targets, to obtain and optimize protein inhibitors, and to determine their underlying biological roles within Mtb. Our multidisciplinary approach has allowed us to add considerable knowledge to mycobacterial structures, and to leverage this information to inform drug development. Significantly, results of the last TBSGC cycle has led to a novel anti-TB drug that is in late pre- clinical development along with others compounds that have been adopted by anti-TB drug developers. In this TBSGC renewal, we propose to incorporate new innovative technologies, including membrane protein structures and cryo-EM, to strengthen our commitment to TB drug development. We will leverage structure determination to both understand function and identify potential small molecule inhibitors. The fundamental goal of this project is to accelerate TB drug discovery by understanding essential functions of the mycobacterial cell and providing validated targets and inhibitors to our partners in the TB drug development community.
项目摘要-整体

项目成果

期刊论文数量(68)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Covalent Inactivation of Mycobacterium tuberculosis Isocitrate Lyase by cis-2,3-Epoxy-Succinic Acid.
顺式 2,3-环氧琥珀酸共价灭活结核分枝杆菌异柠檬酸裂解酶。
  • DOI:
    10.1021/acschembio.0c00740
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Pham,TrucViet;Mellott,DrakeM;Moghadamchargari,Zahra;Chen,Kevin;Krieger,Inna;Laganowsky,Arthur;Sacchettini,JamesC;Meek,ThomasD
  • 通讯作者:
    Meek,ThomasD
Advances In Mycobacterium Tuberculosis Therapeutics Discovery Utlizing Structural Biology.
利用结构生物学发现结核分枝杆菌治疗的进展。
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Chim,Nicholas;Owens,CedricP;Contreras,Heidi;Goulding,CeliaW
  • 通讯作者:
    Goulding,CeliaW
Structural and biochemical analyses of Mycobacterium tuberculosis N-acetylmuramyl-L-alanine amidase Rv3717 point to a role in peptidoglycan fragment recycling.
结核分枝杆菌 N-乙酰胞壁酰-L-丙氨酸酰胺酶 Rv3717 的结构和生化分析表明其在肽聚糖片段回收中发挥作用。
  • DOI:
    10.1074/jbc.m113.510792
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Prigozhin,DaniilM;Mavrici,Daniela;Huizar,JohnP;Vansell,HilaryJ;Alber,Tom
  • 通讯作者:
    Alber,Tom
Optimization of TAM16, a Benzofuran That Inhibits the Thioesterase Activity of Pks13; Evaluation toward a Preclinical Candidate for a Novel Antituberculosis Clinical Target.
  • DOI:
    10.1021/acs.jmedchem.1c01586
  • 发表时间:
    2022-01-13
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
    Wilson C;Ray P;Zuccotto F;Hernandez J;Aggarwal A;Mackenzie C;Caldwell N;Taylor M;Huggett M;Mathieson M;Murugesan D;Smith A;Davis S;Cocco M;Parai MK;Acharya A;Tamaki F;Scullion P;Epemolu O;Riley J;Stojanovski L;Lopez-Román EM;Torres-Gómez PA;Toledo AM;Guijarro-Lopez L;Camino I;Engelhart CA;Schnappinger D;Massoudi LM;Lenaerts A;Robertson GT;Walpole C;Matthews D;Floyd D;Sacchettini JC;Read KD;Encinas L;Bates RH;Green SR;Wyatt PG
  • 通讯作者:
    Wyatt PG
Differentiating the roles of Mycobacterium tuberculosis substrate binding proteins, FecB and FecB2, in iron uptake.
  • DOI:
    10.1371/journal.ppat.1011650
  • 发表时间:
    2023-09
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
  • 通讯作者:
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JAMES C SACCHETTINI其他文献

JAMES C SACCHETTINI的其他文献

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{{ truncateString('JAMES C SACCHETTINI', 18)}}的其他基金

Core B. Biochemistry and Enzymology
核心 B. 生物化学和酶学
  • 批准号:
    10641863
  • 财政年份:
    2020
  • 资助金额:
    $ 238.76万
  • 项目类别:
Core B. Biochemistry and Enzymology
核心 B. 生物化学和酶学
  • 批准号:
    10426177
  • 财政年份:
    2020
  • 资助金额:
    $ 238.76万
  • 项目类别:
Core B. Biochemistry and Enzymology
核心 B. 生物化学和酶学
  • 批准号:
    10190811
  • 财政年份:
    2020
  • 资助金额:
    $ 238.76万
  • 项目类别:
Structure-based Discovery of Critical Vulnerabilities of Micobacteria
基于结构的微生物关键漏洞发现
  • 批准号:
    8711232
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Structure-based Discovery of Critical Vulnerabilities of Micobacteria
基于结构的微生物关键漏洞发现
  • 批准号:
    8534693
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Project 2 - TB Translation as a Target
项目 2 - TB 翻译作为目标
  • 批准号:
    10242864
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Structure-based Discovery of Critical Vulnerabilities of Mycobacteria
基于结构的分枝杆菌关键漏洞发现
  • 批准号:
    9755323
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Structure-based Discovery of Critical Vulnerabilities of Mycobacteria
基于结构的分枝杆菌关键漏洞发现
  • 批准号:
    10242858
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Project 2 - TB Translation as a Target
项目 2 - TB 翻译作为目标
  • 批准号:
    10456894
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:
Admin Core TAMU (Sacchettini) Lead
管理核心 TAMU (Sacchettini) 负责人
  • 批准号:
    10456889
  • 财政年份:
    2012
  • 资助金额:
    $ 238.76万
  • 项目类别:

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