CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

CHAITAN KHOSLA PRT-聚酮化合物的晶体结构

• 批准号: 7721752
• 负责人: CHAITAN KHOSLA
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721752
• 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

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 聚酮合成酶（PKS）产生大量抗癌、抗病毒、降血压和抗生素化合物。 PKS的晶体结构尚未确定。 PKS晶体结构的确定将极大地促进PKS通过蛋白质工程或底物工程的药物利用。 聚酮合酶家族的8个关键酶包括酮合酶/链长因子（KS/CLF）、芳香酶（ARO）、酰基载体蛋白（ACP 4）、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5A 42）的结构已经利用SSRL的射束时间解到2.8 μ m。来自不同物种的TE也被结晶化，这将给我们提供提高TE分辨率的机会。在剩下的七种蛋白质晶体中，发现酮合酶（KS 3）在UCSF的X射线系统下提供有限的分辨率（< 3.5 <$），并且将从SSRL的数据收集中受益匪浅。