CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

CHAITAN KHOSLA PRT-聚酮化合物的晶体结构

• 批准号: 7954171
• 负责人: CHAITAN KHOSLA
• 金额: $ 0.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954171
• 关键词: Acyl Carrier Protein; Antibiotics; Aromatase; Computer Retrieval of Information on Scientific Projects Database; Data; Engineering; Enzymes; FGF4 gene; Family; Funding; Grant; Hypotension; Institution; Length; Malignant Neoplasms; Pharmacologic Substance; Protein Engineering; Proteins; Research; Research Personnel; Resolution; Resources; Source; Structure; System; United States National Institutes of Health; Virus; improved; polyketide synthase; protein structure; structural biology; synchrotron radiation

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. Polyketide synthase (PKS) produces a huge variety of anti-cancer, anti-virus, blood-pressure lowering and antibiotic compounds. No crystal structure has ever been determined for PKS. Determination of crystal structures of PKS will greatly facilitate the pharmaceutical utilization of PKS by protein-engineering or substrate-engineering. Eight critical enzymes of the polyketide synthase family has been crystalized, including ketosynthase/chain length factor (KS/CLF), aromatase (ARO), acyl carrier protein (ACP4), loading didomain (LDD), and various thioesterases (TE). Among these proteins, the structure of thioesterase (TE, proposal 5A42) has been solved to 2.8 ¿ utilizing the beamtime from SSRL. TEs from different species have also been crystallized, and will give us the chance to improve the resolution of TE. Of the remaining seven protein crystals, a ketosynthase (KS3) was found to give limited resolution (< 3.5 ¿) under the x-ray system in UCSF, and will greatly benefit from collecting data at SSRL.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 聚酮化合物合酶（PKS）产生各种抗癌，抗病毒，血压降低和抗生素化合物。尚未确定PKS的晶体结构。 PK的晶体结构的测定将通过蛋白质工程或底物工程技术极大地支持PK的药物利用。聚酮化合物合酶家族的八种关键酶已经结晶，包括酮非酶/链长度因子（KS/CLF），芳香酶（ARO），酰基载体蛋白（ACP4），加载didomain（LDD）和各种硫酯酶（TE）。在这些蛋白质中，使用SSRL的Beamtime解决了硫酯酶的结构（TE，提案5A42）。来自不同物种的TE也已经结晶，将使我们有机会改善TE分辨率。在其余七个蛋白质晶体中，发现在UCSF的X射线系统下，酮合酶（KS3）在X射线系统下得出有限的分辨率（<3.5？），并且将从SSRL收集数据中受益匪浅。