Collaborative Research: Structure and function of flavin-dependent N-monooxygenases

合作研究：黄素依赖性 N-单加氧酶的结构和功能

基本信息

批准号：
2003658
负责人：
Pablo Sobrado
金额：
$ 33万
依托单位：
Virginia Polytechnic Institute and State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003658&HistoricalAwards=false
关键词：
Collaborative Research Structure function flavin

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Pablo Sobrado from Virginia Tech and John. J. Tanner from the University of Missouri to investigate the structure and chemistry of enzymes known as flavin-dependent-N-monooxygenases (NMOs). NMOs play integral parts in how microorganisms make numerous natural compounds for a variety of purposes. These compounds can also have useful bioactivities that benefit society. While many flavin-dependent enzymes are well known and have been thoroughly characterized, the NMOs are a relatively recently discovered branch on the family tree, and do not resemble the other members in common ways. This leads to the hypothesis that new and interesting structures and chemistries are likely to be at play in the reactions catalyzed by the NMOs. The investigators choose several examples of NMOs for in depth examination in order to compare and contrast their behaviors. Further, a highly multidisciplinary approach is proposed to provide the broadest possible understanding of the enzymes. The proposed experimental approach will provide a platform for the training of undergraduate and graduate students in modern enzymology and biophysical chemistry. The laboratories are also committed to strategies to enhance diversity in the scientific research workforce.This project expands our knowledge of the diversity of flavoenzymes through the structural and biochemical characterization of new N-monooxygenases. Because these enzymes have low similarity to proteins already in the Protein Data Bank, the structures are expected to exhibit novel features and reveal unanticipated relationships to other enzymes. This further advances our understanding of the evolutionary relatedness of these enzymes. Also addressed are key knowledge gaps in our understanding of flavoenzyme mechanisms by characterizing “double-hydroxylating” NMOs, exploring a newly discovered flavin “flapping” motion in Group B NMOs, and trapping heretofore-elusive flavoenzyme-ligand complexes in crystallo for structure determination.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学部门的化学过程计划正在为弗吉尼亚理工大学和约翰的Pablo Sobrado博士提供资金。密苏里大学的J.坦纳（J. Tanner）研究了称为黄素依赖性-N-共氧酶（NMOS）的酶的结构和化学。 NMO在微生物如何制造出多种天然化合物的方式中发挥不可或缺的作用。这些化合物还可以具有有益的生物活性，从而使社会受益。尽管许多依赖黄素的酶是众所周知的，并且已经彻底表征了，但NMOS是家族树上相对较新的分支，并不像其他常见成员一样类似于其他成员。这导致了以下假设：新的和有趣的结构和化学可能在NMO催化的反应中起作用。研究人员选择了一些NMO的示例进行深入检查，以比较和对比其行为。此外，提出了一种高度多学科的方法，以提供对酶的最广泛的理解。拟议的实验方法将为培训现代酶学和生物物理化学研究生的本科生和研究生提供一个平台。实验室还致力于提高科学研究劳动力的多样性策略。该项目通过新的N-偶氮酶的结构和生化表征扩大了我们对黄酮酶多样性的了解。由于这些酶与蛋白质数据库中已经已经存在的蛋白质相似，因此预期结构会发现新的特征并揭示与其他酶的意外关系。这进一步提高了我们对这些酶进化相关性的理解。我们还通过表征“双重羟基化” NMO来理解我们对黄酮酶机制的关键知识差距。基金会的智力优点和更广泛的影响审查标准。