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. A detailed understanding of the dynamics of a protein can greatly aid in understanding and manipulating its function. Detailed nuclear magentic resonance (NMR) experiments provide experimental evidence of the importance of backbone and sidechain movements in a number of systems. We have recently developed a new method to analyze electron density maps from crystallographic experiments that enables assessment of the conformational entropy of the amino acid side chain at each position of the structure: the tau value. In order to validate this measure, which works best with ultra-high resolution structures, we have chosen experimental systems where both backbone and side chain movements are well characterized by NMR experiments: the human peptidyl proline isomerase (CypA) and a receiver domain of the regulator of social motility in Myxococcus xanthus (FrzS). Comparing the CypA structure to previously solved structures in multiple states of ligand binding, and comparing FrzS variants to other homologous receiver domains will further our investigations into correlating dynamic measurements to our new metric that samples electron density directly to determine conformational entropy. We have obtained crystals for both systems, and request beam time at SSRL to collect ultra-high resolution, and, in the case of FrzS variant I82M, MAD data sets.
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