STRUCTURAL BIOLOGY OF SMALL MOLECULE SENSORS, CHANNELS AND ACTIVATORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 我们的实验室对一些以小分子的激活、运输和传感为中心的项目感兴趣。一个研究重点集中在与吡咯赖氨酸（第22种遗传编码的氨基酸）激活一甲胺相关的过程。吡咯赖氨酸是基于使用SSRL收集的数据对巴氏甲烷八叠球菌单甲胺甲基转移酶的结构测定而发现的。我们希望通过确定二甲胺和三甲胺激活相关的含吡咯赖氨酸的蛋白质的结构来继续这个项目，以了解其独特特异性的起源。虽然这些甲基转移酶在功能上相似，但它们彼此没有表现出明显的同源性。吡咯赖氨酸区域内的一个相关靶标是吡咯赖氨酰tRNA合成酶的结构决定，该合成酶用吡咯赖氨酸装载pyl-tRNA。第二个研究重点是阐明参与小分子，特别是CO2和O2的运输和传感的蛋白质。其中一些是膜蛋白。SSRL的射束时间将用于促进这些蛋白质的结构测定。

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. Our laboratory is interested in a number of projects centered on the activation, transport and sensing of small molecules. One research focus centers on the processes associated with monomethylamine activation by pyrrolysine, the 22nd genetically-encoded amino acid. Pyrrolysine was discovered based on the structure determination of the Methanosarcina barkeri monomethylamine methyltransferase using data collected at SSRL. We wish to continue this project by determining the structures of the related pyrrolysine containing proteins involved in dimethylamine and trimethylamine activation to understand the origin of their distinct specificities. While these methyltransferases are functionally similar they exhibit no apparent homology with one another. A related target within the pyrrolysine area is the structural determination of the pyrrolysyl tRNA synthetase that charges pyl-tRNA with pyrrolysine. A second research focus is the elucidation of proteins involved in the transport and sensing of small molecules, particularly CO2 and O2. Some of these are membrane proteins. The beamtime at SSRL will be used to facilitate the structural determination of these proteins.