STRUCTURAL BIOLOGY OF SMALL MOLECULE SENSORS, CHANNELS AND ACTIVATORS

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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.