STRUCTURE OF A NOVEL OXIDOREDUCTASE (TETX) IN TETRACYCLINE DRUG RESISTANCE

一种新型氧化还原酶（TETX）在四环素耐药性中的结构

• 批准号: 7721323
• 负责人: Yousif Shamoo
• 金额: $ 2.09万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721323
• 关键词: Agriculture; Animal Feed; Antibiotics; Chlamydia; Chlortetracycline; Class; Clinical; Collection; Complex; Computer Retrieval of Information on Scientific Projects Database; Condition; Crystallization; Data; Data Set; Drug Efflux; Drug resistance; Freezing; Funding; Grant; Growth; Institution; Mycoplasma; Numbers; Oxidoreductase; Oxytetracycline; Pharmaceutical Preparations; Proteins; Range; Research; Research Personnel; Resistance; Resources; Source; Structure; Tetracycline; Tetracyclines; Therapeutic; United States Food and Drug Administration; United States National Institutes of Health; bacterial resistance; member; novel; resistance mechanism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since their discovery in the 1940s, the tetracycline class of antibiotics has been widely used against a broad range of Gram positive, Gram negative and more unusual targets such as Chlamydia and mycoplasmas. In addition to classic medicinal applications, chlortetracycline and oxytetracycline are commonly used at sub-therapeutic levels in animal feed as growth. As the tetracyclines have risen to become the most widely produced antibiotic, the number of resistant bacteria has increased to the point that they are nearly ubiquitous in clinical and agricultural settings. Resistance is typically conferred by either efflux of the drug (tetA) or ribsomal protection (tetM and tetO). Recently, a new enzymatic mechanism of resistance was discovered through drug inactivation (tetX). We have found crystallization conditions for tetX and are requesting beamtime for the collection of a MAD data set. Very small native crystals diffracted to 2.6 A at CHESS F1 (the crystal was shot by a colleague but was unable to collect data because of poor freezes). These freezing issues have since been resolved. We would like to collect both a native and MAD data set of the tetX protein as well as a soak of the drug-complex. Our studies are particularly relevant as one of the most recent antibiotics approved by the FDA is Tygacil¿¿ or tigilcycline, a member of the tetracycline class is readily inactivated by tetX.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 自 20 世纪 40 年代发现以来，四环素类抗生素已广泛用于对抗各种革兰氏阳性、革兰氏阴性和更不寻常的靶标，例如衣原体和支原体。除了经典的医学应用外，金霉素和土霉素也常用于治疗。随着四环素已成为生产最广泛的抗生素，动物饲料中的亚治疗水平也随之增加。它们在临床和农业环境中几乎无处不在，通常是由药物外流（tetA）或核体保护（tetM 和 tetO）产生的。最近，通过药物失活（tetX）发现了一种新的酶促耐药机制。 ）我们已经找到了 tetX 的结晶条件，并要求收集衍射至 2.6 A 的非常小的原生晶体。在 CHESS F1 中（晶体被同事拍摄，但由于冷冻效果不佳而无法收集数据）。我们希望收集 tetX 蛋白的原生数据集和 MAD 数据集。我们的研究特别相关，因为 FDA 批准的最新抗生素之一是 Tygacil。 ¿或替吉环素（四环素类成员）很容易被 tetX 灭活。