SAXS OF METHYLAMINE DEHYDROGENASE ELECTRON TRANSFER PROTEIN COMPLEXES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定为研究者机构。甲胺脱氢酶（MADH）是一种古老的细菌代谢酶，在有氧世界之前进化。它的厌氧起源是由它催化的高度进化的多步化学反应，以及它在催化过程中使用辅助氧化还原蛋白质伴侣而不是分子氧来去除电子所证明的。通过这些类型的电子转移反应产生的能量是生物体中所有能量产生的基础。虽然是趋同进化的产物，但该酶催化的还原化学类似于含铜胺氧化酶家族，其人类对应物与晚期糖尿病并发症和充血性心脏病的血管变化有关。 使用单晶可见光谱，X射线晶体学和冷冻捕获，以及小角X射线散射的新组合，该项目将探索蛋白质如何通过捕获含晶体的Paracoccus MADH（PD-MADH）中的催化中间体来控制其复杂的多步反应，并确定其结构。通过研究这个高度发达的代谢系统，一个古老的厌氧氧化还原化学的一部分，今天仍然存在于线粒体和叶绿体中，我们可以揭示利用能量和材料的基本过程，这些过程在地球上进化出复杂的生命。

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. Methylamine dehydrogenase (MADH) is an ancient bacterial metabolic enzyme that evolved in a pre-aerobic world. Its anaerobic origins are attested to by the highly evolved multistep chemistry it catalyzes, and its use of ancillary redox protein partners, rather than molecular oxygen, to remove electrons during catalysis. The energy generated through these types of electron transfer reactions underlies all energy generation in living organisms. Although a product of convergent evolution, the reductive chemistry catalyzed by the enzyme is analogous to that of the copper-containing amine oxidase family, whose human counterparts are linked to late-diabetic complications and vascular changes in congestive heart disease. Using a novel combination of single crystal visible spectroscopy, X-ray crystallography and freeze-trapping, and small-angle X-ray scattering, this project will probe how the protein controls its complex multistep reaction at atomic resolution by trapping catalytic intermediates in Paracoccus denitrificans MADH (PD-MADH) containing crystals, and determining their structures. By studying this highly developed metabolic system, a part of the ancient anaerobic redox chemistries still found in mitochondria and chloroplasts today, we can shed light on the fundamental processes of harnessing energy and materials that evolved complex life on earth.