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. Wide-angle x-ray solution scattering (WAXS) has significant potential for characterizing the structure, dynamics and function of proteins without the need for crystallization (Fischetti et al., 2003). We have carried out a theoretical analysis of the information content of WAXS and quantitated its capabilities for determining the secondary and tertiary structure of a protein (Makowski et al., 2008a). Using WAXS from proteins at different concentrations or temperatures, we demonstrated that WAXS contains substantial information about the structural fluctuations within an ensemble of proteins (Makowski et al., 2008b). We have further shown that the amplitudes of normal modes of motion of a protein can be estimated using WAXS (Park and Makowski, 2008). We have carried out the first measurement of the anomalous signal from proteins in solution, and demonstrated that it can be used to measure interatomic distances within proteins (Fischetti et al., 2008), including membrane proteins (Makowski et al., 2008c). Its power for measurement of small structural changes makes it an excellent tool for screening of functional binding events (Rodi et al., 2007). The goal of the present request is to continue data collection on a number of projects that will expand and develop these recent successes. In particular, we will carry out several related projects that will utilize WAXS for the study of the structure and dynamics of proteins, including: (i) A detailed analysis of the effect of mutations on the dynamic behavior of HIV protease; (ii) Estimation of the breadth of molecular motion during catalysis of HIV protease;(iii) Analysis of the effect of ligand state and mutations on the dynamic behavior of hemoglobin; (iv) analysis of the structural changes that occur during ligand binding and catalytic activity of adenylate kinase.
| Orgel, Joseph P R O; Sella, Ido; Madhurapantula, Rama S et al. (2017) Molecular and ultrastructural studies of a fibrillar collagen from octocoral (Cnidaria). J Exp Biol 220:3327-3335 |
| Yazdi, Aliakbar Khalili; Vezina, Grant C; Shilton, Brian H (2017) An alternate mode of oligomerization for E. coli SecA. Sci Rep 7:11747 |
| Sullivan, Brendan; Robison, Gregory; Pushkar, Yulia et al. (2017) Copper accumulation in rodent brain astrocytes: A species difference. J Trace Elem Med Biol 39:6-13 |
| Morris, Martha Clare (2016) Nutrition and risk of dementia: overview and methodological issues. Ann N Y Acad Sci 1367:31-7 |
| Robison, Gregory; Sullivan, Brendan; Cannon, Jason R et al. (2015) Identification of dopaminergic neurons of the substantia nigra pars compacta as a target of manganese accumulation. Metallomics 7:748-55 |
| Gelfand, Paul; Smith, Randy J; Stavitski, Eli et al. (2015) Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed FTIR Imaging. Anal Chem 87:6025-31 |
| Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-1358 |
| Zhou, Hao; Li, Shangyang; Badger, John et al. (2015) Modulation of HIV protease flexibility by the T80N mutation. Proteins 83:1929-39 |
| Nobrega, R Paul; Arora, Karunesh; Kathuria, Sagar V et al. (2014) Modulation of frustration in folding by sequence permutation. Proc Natl Acad Sci U S A 111:10562-7 |
| Jiao, Lianying; Ouyang, Songying; Shaw, Neil et al. (2014) Mechanism of the Rpn13-induced activation of Uch37. Protein Cell 5:616-30 |
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