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.Prephenate dehydrogenase: The first committed step in tyrosine biosynthesis is the oxidative decarboxylation of prephenate to p-hydroxylphenylpyruvate (HPP). This reaction is catalyzed by prephenate dehydrogenase in the presence of NAD+ [1]. This enzyme is of paramount importance since it channels prephenate, a branch point intermediate in tyrosine and phenylalanine biosynthesis, to tyrosine synthesis. The biosynthesis of tyrosine is of critical importance for the growth and survival of enteric bacteria, yeasts, fungi and plants. Like the other aromatic amino acids, tyrosine plays dual roles in the biochemistry of the organism, acting as both a product and a precursor. In the former case, tyrosine is required for protein synthesis, whereas, in the latter example, it is a substrate for enzymes in downstream metabolic pathways. The aromatic metabolites derived from tyrosine include quinones [2, 3], cyanogenic glycosides [4], alkaloids [5, 6], flavonoids [7], and phenolic compounds derived from the phenylpropanoid pathway [7, 8]. Since many of these compounds are involved in primary biological processes, they are essential for viability. In plants, for example, flavonoids are important for normal development as they are involved in auxin transport [9-11], pollen germination [9, 12, 13], and signaling to symbiotic microorganisms [9, 14]. We have recently determined the crystal structure of prephenate dehydrogenase however we propose that our understanding of the mechanism of this enzyme hinges on determining its crystal structure in complex with know ligands. We recently obtained crystals of prephenate dehydrogenase in co-crystallization studies using prephenate, (4-hydroxyphenyl)pyruvate and tyrosine separately. We are requesting beam time for x-ray data collection to determine the structure of prephenate dehydrogenase in complex with these ligands.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-25
Application #
7598551
Study Section
Special Emphasis Panel (ZRG1-BBCA (40))
Project Start
2007-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
25
Fiscal Year
2007
Total Cost
$16,163
Indirect Cost
Name
Cornell University
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Kozlov, Guennadi; Wong, Kathy; Gehring, Kalle (2018) Crystal structure of the Legionella effector Lem22. Proteins 86:263-267
Ménade, Marie; Kozlov, Guennadi; Trempe, Jean-François et al. (2018) Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide insight into pathological mutations. J Biol Chem 293:12832-12842
Xu, Jie; Kozlov, Guennadi; McPherson, Peter S et al. (2018) A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy. J Biol Chem 293:4566-4574
Dean, Dexter N; Rana, Pratip; Campbell, Ryan P et al. (2018) Propagation of an A? Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate. Biophys J 114:539-549
Chen, Yu Seby; Kozlov, Guennadi; Fakih, Rayan et al. (2018) The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg2+ efflux activity. J Biol Chem 293:19998-20007
Xu, Caishuang; Kozlov, Guennadi; Wong, Kathy et al. (2016) Crystal Structure of the Salmonella Typhimurium Effector GtgE. PLoS One 11:e0166643
Cogliati, Massimo; Zani, Alberto; Rickerts, Volker et al. (2016) Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population. Fungal Genet Biol 87:22-9
Oot, Rebecca A; Kane, Patricia M; Berry, Edward A et al. (2016) Crystal structure of yeast V1-ATPase in the autoinhibited state. EMBO J 35:1694-706
Lucido, Michael J; Orlando, Benjamin J; Vecchio, Alex J et al. (2016) Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. Biochemistry 55:1226-38
Bauman, Joseph D; Harrison, Jerry Joe E K; Arnold, Eddy (2016) Rapid experimental SAD phasing and hot-spot identification with halogenated fragments. IUCrJ 3:51-60

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