CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

CHAITAN KHOSLA PRT-聚酮化合物的晶体结构

• 批准号: 8362042
• 负责人: CHAITAN KHOSLA
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362042
• 关键词: Acyl Carrier Protein; Antibiotics; Aromatase; Data; Engineering; Enzymes; FGF4 gene; Family; Funding; Grant; Hypotension; Length; Malignant Neoplasms; National Center for Research Resources; Pharmacologic Substance; Principal Investigator; Protein Engineering; Proteins; Radiation; Research; Research Infrastructure; Resolution; Resources; Source; Structure; System; United States National Institutes of Health; Virus; cost; improved; polyketide synthase; protein structure; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 聚酮合酶（PKS）可产生多种抗癌、抗病毒、降血压和抗生素化合物。目前尚未确定PKS的晶体结构。PKS晶体结构的测定将极大地促进PKS的药物利用。通过蛋白质工程或底物工程，聚酮合酶家族的八种关键酶已结晶，包括酮合酶/链长因子（KS/CLF）、芳香酶（ARO）、酰基载体蛋白（ACP4）、负载双结构域（LDD）和各种硫酯酶（TE）在这些蛋白质中，硫酯酶（TE，提案5A42）的结构已解析为2.8 ¿利用来自不同物种的 TE 也已结晶，这将使我们有机会提高其余七种蛋白质晶体的分辨率，发现酮合酶 (KS3) 的分辨率有限（< 3.5 ¿ ）在 UCSF 的 X 射线系统下，并且将从 SSRL 收集的数据中受益匪浅。