CHAITAN KHOSLA PRT-CRYSTAL STRUCTURES OF POLYKETIDE

CHAITAN KHOSLA PRT-聚酮化合物的晶体结构

• 批准号: 7370401
• 负责人: CHAITAN KHOSLA
• 金额: $ 0.36万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370401
• 关键词: CHAITAN; KHOSLA; PRT; CRYSTAL; STRUCTURES

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.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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的束流时间解析为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，发现了一种酮合成酶(KS3)，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。