This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Human DJ-1 plays an important role in the cellular response to oxidative stress, and certain point mutations in DJ-1 have been associated with rare forms of autosomal recessive early-onset Parkinson?s disease. In addition, DJ-1 was independently discovered as a ras-dependent oncogene and has been implicated in certain types of cancer. Studies by us and others have revealed that DJ-1 is a homodimer that contains a highly conserved cysteine residue with a depressed pKa value that is essential for DJ-1?s protective activity. Based on a previous atomic resolution structure of human DJ-1, we have made and crystallized a number of point mutants that alter the reactivity of this functionally critical cysteine residue in DJ-1. We propose to determine the X-ray crystal structures of these mutants in order to provide a clear structural explanation for our completed biochemical study of cysteine reactivity in DJ-1. The principal goal of the proposed work is to identify the structural determinants of cysteine reactivity in human DJ-1. In addition, we are undertaking the structural characterization of a new member of the DJ-1 superfamily from plants. Unlike all other characterized members of the DJ-1 superfamily, plant DJ-1 is predicted to be a pseudo-dimeric monomer with unique structural features. We will determine the X-ray crystal structure of a representative plant DJ-1 protein and use these results to form testable hypotheses about the function of plant DJ-1 proteins. These experiments are part of an ongoing effort to comprehensively characterize the function of eukaryotic DJ-1 from several different model organisms.
| Weingarten, Adam S; Dannenhoffer, Adam J; Kazantsev, Roman V et al. (2018) Chromophore Dipole Directs Morphology and Photocatalytic Hydrogen Generation. J Am Chem Soc 140:4965-4968 |
| Yang, Cheolhee; Choi, Minseo; Kim, Jong Goo et al. (2018) Protein Structural Dynamics of Wild-Type and Mutant Homodimeric Hemoglobin Studied by Time-Resolved X-Ray Solution Scattering. Int J Mol Sci 19: |
| Kazantsev, Roman V; Dannenhoffer, Adam J; Weingarten, Adam S et al. (2017) Crystal-Phase Transitions and Photocatalysis in Supramolecular Scaffolds. J Am Chem Soc 139:6120-6127 |
| Fournier, Bertrand; Sokolow, Jesse; Coppens, Philip (2016) Analysis of multicrystal pump-probe data sets. II. Scaling of ratio data sets. Acta Crystallogr A Found Adv 72:250-60 |
| Cho, Hyun Sun; Schotte, Friedrich; Dashdorj, Naranbaatar et al. (2016) Picosecond Photobiology: Watching a Signaling Protein Function in Real Time via Time-Resolved Small- and Wide-Angle X-ray Scattering. J Am Chem Soc 138:8815-23 |
| Pande, Kanupriya; Hutchison, Christopher D M; Groenhof, Gerrit et al. (2016) Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein. Science 352:725-9 |
| Weingarten, Adam S; Kazantsev, Roman V; Palmer, Liam C et al. (2015) Supramolecular Packing Controls H? Photocatalysis in Chromophore Amphiphile Hydrogels. J Am Chem Soc 137:15241-6 |
| Pfoh, Roland; Pai, Emil F; Saridakis, Vivian (2015) Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides. Acta Crystallogr D Biol Crystallogr 71:2032-9 |
| Mariette, Céline; Guérin, Laurent; Rabiller, Philippe et al. (2015) The creation of modulated monoclinic aperiodic composites in n-alkane/urea compounds. Z Kristallogr Cryst Mater 230:5-11 |
| Yang, Xiaojing; Stojkovi?, Emina A; Ozarowski, Wesley B et al. (2015) Light Signaling Mechanism of Two Tandem Bacteriophytochromes. Structure 23:1179-89 |
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