CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 聚酮合成酶(PKS)能产生多种抗癌、抗病毒、降血压和抗菌化合物。目前还没有确定PKS的晶体结构。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。聚酮合成酶家族的8个关键酶已被结晶，包括酮合成酶/链长因子(KS/CLF)、芳香酶(ARO)、酰基载体蛋白(ACP4)、负载双域(LDD)和各种硫代酯酶(TE)。在这些蛋白质中，硫代酯酶(TE，建议5A42)的结构已经利用SSRL的束流时间解析到2.8°。来自不同物种的TE也已经结晶，这将使我们有机会提高TE的分辨率。在剩下的七种蛋白质晶体中，一种酮合成酶(KS3)被发现在加州大学旧金山分校的X射线系统下分辨率有限(&lt；3.5？)，这将极大地受益于SSRL的数据收集。

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.