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| | <StructureSection load='6yk0' size='340' side='right'caption='[[6yk0]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='6yk0' size='340' side='right'caption='[[6yk0]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YK0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yk0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YK0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YK0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pdxk, Pkh ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.35 2.7.1.35] </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=6yk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yk0 OCA], [https://pdbe.org/6yk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yk0 RCSB], [https://www.ebi.ac.uk/pdbsum/6yk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yk0 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=6yk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yk0 OCA], [https://pdbe.org/6yk0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yk0 RCSB], [https://www.ebi.ac.uk/pdbsum/6yk0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yk0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PDXK_MOUSE PDXK_MOUSE]] Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (By similarity). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions (By similarity).[UniProtKB:O00764]
| + | [https://www.uniprot.org/uniprot/PDXK_MOUSE PDXK_MOUSE] Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (By similarity). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions (By similarity).[UniProtKB:O00764] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Pyridoxal kinase]]
| + | [[Category: Kasaragod VB]] |
| - | [[Category: Kasaragod, V B]] | + | [[Category: Schindelin H]] |
| - | [[Category: Schindelin, H]] | + | |
| - | [[Category: Atp gamma s]]
| + | |
| - | [[Category: Pdxk]]
| + | |
| - | [[Category: Plp]]
| + | |
| - | [[Category: Pyridoxal]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PDXK_MOUSE Catalyzes the phosphorylation of the dietary vitamin B6 vitamers pyridoxal (PL), pyridoxine (PN) and pyridoxamine (PM) to form pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP) and pyridoxamine 5'-phosphate (PMP), respectively (By similarity). PLP is the active form of vitamin B6, and acts as a cofactor for over 140 different enzymatic reactions (By similarity).[UniProtKB:O00764]
Publication Abstract from PubMed
The antimalarial artemisinins have also been implicated in the regulation of various cellular pathways including immunomodulation of cancers and regulation of pancreatic cell signaling in mammals. Despite their widespread application, the cellular specificities and molecular mechanisms of target recognition by artemisinins remain poorly characterized. We recently demonstrated how these drugs modulate inhibitory postsynaptic signaling by direct binding to the postsynaptic scaffolding protein gephyrin. Here, we report the crystal structure of the central metabolic enzyme pyridoxal kinase (PDXK), which catalyzes the production of the active form of vitamin B6 (also known as pyridoxal 5'-phosphate [PLP]), in complex with artesunate at 2.4-A resolution. Partially overlapping binding of artemisinins with the substrate pyridoxal inhibits PLP biosynthesis as demonstrated by kinetic measurements. Electrophysiological recordings from hippocampal slices and activity measurements of glutamic acid decarboxylase (GAD), a PLP-dependent enzyme synthesizing the neurotransmitter gamma-aminobutyric acid (GABA), define how artemisinins also interfere presynaptically with GABAergic signaling. Our data provide a comprehensive picture of artemisinin-induced effects on inhibitory signaling in the brain.
Pyridoxal kinase inhibition by artemisinins down-regulates inhibitory neurotransmission.,Kasaragod VB, Pacios-Michelena A, Schaefer N, Zheng F, Bader N, Alzheimer C, Villmann C, Schindelin H Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33235-33245. doi:, 10.1073/pnas.2008695117. Epub 2020 Dec 14. PMID:33318193[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kasaragod VB, Pacios-Michelena A, Schaefer N, Zheng F, Bader N, Alzheimer C, Villmann C, Schindelin H. Pyridoxal kinase inhibition by artemisinins down-regulates inhibitory neurotransmission. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33235-33245. doi:, 10.1073/pnas.2008695117. Epub 2020 Dec 14. PMID:33318193 doi:http://dx.doi.org/10.1073/pnas.2008695117
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