Yeast nicotinate-nucleotide pyrophosphorylase in complex with ligand: crystallization and preliminary structural approaches

다국어 초록 (Multilingual Abstract)

Pyridine-2,3-dicarboxylic acid which is a biologically potent molecule implicated in the neurodegenerative environment is catalyzed by nicotinate-nucleotide pyrophosphorylase (NMnPP) to produce a precursor molecule, nicotinate mononucleotide (NMn), of de novo biosynthesis of the coenzyme nicotinamide adenine dinucleotide (NAD+). The protein preparation, crystallization, and preliminary structural features of full-length enzyme in complex with product reactant suggest that yeast NMnPP acts as stable hexamer formation. Crystals of S. cerevisiae NMnPP were obtained and diffracted to a resolution of 1.74 Å and 1.99 Å for apo and complex forms, belonged to the trigonal symmetry group R32 in the unit-cell parameters of a = b = 155.313, c = 67.507 and a = b = 155.091, c = 69.204, respectively. Based on our comparison of eukaryotic NMnPP structures in the apo and complex forms, we propose functional and structural investigation for product binding and hexamer stabilization.

참고문헌 (Reference)

1 Kim, M. K., "The role of Phe181 in the hexamerization of Helicobacter pylori quinolinate phosphoribosyltransferase" 26 : 517-521, 2007

2 Sahm, F., "The endogenous tryptophan metabolite and NAD+precursor quinolinic acid confers resistance of gliomas to oxidative stress" 73 : 3225-3234, 2013

3 Youn, H. S., "Structural insights into the quaternary catalytic mechanism of hexameric human quinolinate phosphoribosyltransferase, a key enzyme in de novo NAD biosynthesis" 6 : 19681-, 2016

4 Liu, H., "Structural and kinetic characterization of quinolinate phosphoribosyltransferase(hQPRTase)from homo sapiens" 373 : 755-763, 2007

5 McCoy, A. J., "Solving structures of protein complexes by molecular replacement with Phaser" 63 : 32-41, 2007

6 Matthews, B. W., "Solvent content of protein crystals" 33 : 491-497, 1968

7 Amjad, S., "Role of NAD+ in regulating cellular and metabolic signaling pathways" 49 : 101195-, 2021

8 Guillemin, G. J., "Quinolinic acid selectively induces apoptosis of human astrocytes : potential role in AIDS dementia complex" 2 : 16-, 2005

9 Otwinowski, Z., "Processing of X-ray diffraction data collected in oscillation mode" 276 : 307-326, 1997

10 Adams, P. D., "PHENIX : a comprehensive Python-based system for macromolecular structure solution" 66 : 213-221, 2010

11 Vagin, A., "Molecular replacement with MOLREP" 66 : 22-25, 2010

12 Vega-Naredo, I., "Melatonin neutralizes neurotoxicity induced by quinolinic acid in brain tissue culture" 39 : 266-275, 2005

13 Guillemin, G. J., "Indoleamine 2, 3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus" 31 : 395-404, 2005

14 Kim, M. K., "Crystal structure of quinolinic acid phosphoribosyltransferase from Helicobacter pylori" 63 : 252-255, 2006

15 Youn, H. S., "Crystal structure of Sus scrofa quinolinate phosphoribosyl transferase in complex with nicotinate mononucleotide" 8 : e62027-, 2013

16 Emsley, P., "Coot : model-building tools for molecular graphics" 60 : 2126-2132, 2004

17 Di Luccio, E., "Comprehensive X-ray structural studies of the quinolinate phosphoribosyl transferase(BNA6)from Saccharomyces cerevisiae" 47 : 4039-4050, 2008

18 Beal, M. F., "Chronic quinolinic acid lesions in rats closely resemble Huntington’s disease" 11 : 1649-1659, 1991

19 Braidy, N., "Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats" 278 : 4425-4434, 2011

20 Opitz, C. A., "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor" 478 : 197-203, 2011