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| | <StructureSection load='2qsz' size='340' side='right'caption='[[2qsz]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='2qsz' size='340' side='right'caption='[[2qsz]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qsz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QSZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qsz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QSZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QSZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NMN:BETA-NICOTINAMIDE+RIBOSE+MONOPHOSPHATE'>NMN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qsy|2qsy]], [[2qt0|2qt0]], [[2qt1|2qt1]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NRK1, C9orf95 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qsz OCA], [https://pdbe.org/2qsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qsz RCSB], [https://www.ebi.ac.uk/pdbsum/2qsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qsz ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qsz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qsz OCA], [https://pdbe.org/2qsz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qsz RCSB], [https://www.ebi.ac.uk/pdbsum/2qsz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qsz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NRK1_HUMAN NRK1_HUMAN]] Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine.<ref>PMID:15137942</ref>
| + | [https://www.uniprot.org/uniprot/NRK1_HUMAN NRK1_HUMAN] Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine.<ref>PMID:15137942</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Brenner, C]] | + | [[Category: Brenner C]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Edwards AM]] |
| - | [[Category: Landry, R]] | + | [[Category: Landry R]] |
| - | [[Category: Nedyalkova, L]] | + | [[Category: Nedyalkova L]] |
| - | [[Category: Park, H]] | + | [[Category: Park H]] |
| - | [[Category: Rabeh, W M]] | + | [[Category: Rabeh WM]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sundstrom M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Tempel W]] |
| - | [[Category: Tempel, W]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Adp]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Nad biosynthesis]]
| + | |
| - | [[Category: Nad+]]
| + | |
| - | [[Category: Nicotinamide riboside]]
| + | |
| - | [[Category: Nicotinamide riboside kinase activity]]
| + | |
| - | [[Category: Nicotinic acid riboside kinase activity]]
| + | |
| - | [[Category: Non-protein kinase]]
| + | |
| - | [[Category: Nrk1]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Pyridine nucleotide biosynthesis]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
2qsz is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.9Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
NRK1_HUMAN Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The eukaryotic nicotinamide riboside kinase (Nrk) pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+) by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.
Nicotinamide riboside kinase structures reveal new pathways to NAD+.,Tempel W, Rabeh WM, Bogan KL, Belenky P, Wojcik M, Seidle HF, Nedyalkova L, Yang T, Sauve AA, Park HW, Brenner C PLoS Biol. 2007 Oct 2;5(10):e263. PMID:17914902[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell. 2004 May 14;117(4):495-502. PMID:15137942
- ↑ Tempel W, Rabeh WM, Bogan KL, Belenky P, Wojcik M, Seidle HF, Nedyalkova L, Yang T, Sauve AA, Park HW, Brenner C. Nicotinamide riboside kinase structures reveal new pathways to NAD+. PLoS Biol. 2007 Oct 2;5(10):e263. PMID:17914902 doi:10.1371/journal.pbio.0050263
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