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. We propose to use X-ray crystallography to study conformational changes of an allosteric protein, rabbit muscle pyruvate kinase (M1-PYK) that are important to the allosteric mechanism. Despite the importance of allosteric regulation in allowing biological systems to adapt to changing environments, the molecular mechanisms of allostery are poorly understood. Our results with allosteric effectors of M1-PYK demonstrate that discrete substructures within the inhibitor, phenylalanine, have functionally specific roles, that is, substructures required for binding differ from those that elicit an allosteric response (Williams et al. (2006) Biochemistry 45, 5421-5429). The resulting hypothesis is that the protein properties that are altered upon effector binding must also be divided into the same functional subsets. Using this information, serine and alanine can be considered as non-allosteric effector analogs, analogs that bind competitively with phenylalanine but do not elicit an allosteric response. 2-amino butyric acid elicits a modest allosteric inhibition as compared to phenylalanine. Small-angle X-ray scattering data indicate that the global conformational changes observed when phenylalanine binds are also elicited when non-allosteric effector analogs bind. As such, these global changes may be confined to binding functions. Higher resolution data than are possible with SAXS are needed to characterize small differences between the changes elicited by different effector analogs. These small differences are likely consequential to allosteric functions. We have previously solved the structure of M1-PYK in complex with Ala at 1.65? (Williams et al. (2006) Biochemistry 45, 5421-5429). The current beamtime request will be used to collect data for the structures of M1-PYK co-crystalized with phenylalanine, 2-amino butyric acid, and serine.
| 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: |
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| 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 |
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| 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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