CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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。

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.