4en4: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4en4]] is a 2 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=4EN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EN4 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4en4]] is a 2 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=4EN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EN4 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GT0:5-(HYDROXYMETHYL)-4-(METHOXYMETHYL)-2-METHYLPYRIDIN-3-OL'>GT0</scene>, <scene name='pdbligand=GT1:[5-HYDROXY-4-(METHOXYMETHYL)-6-METHYLPYRIDIN-3-YL]METHYL+DIHYDROGEN+PHOSPHATE'>GT1</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GT0:5-(HYDROXYMETHYL)-4-(METHOXYMETHYL)-2-METHYLPYRIDIN-3-OL'>GT0</scene>, <scene name='pdbligand=GT1:[5-HYDROXY-4-(METHOXYMETHYL)-6-METHYLPYRIDIN-3-YL]METHYL+DIHYDROGEN+PHOSPHATE'>GT1</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4en4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4en4 OCA], [https://pdbe.org/4en4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4en4 RCSB], [https://www.ebi.ac.uk/pdbsum/4en4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4en4 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=4en4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4en4 OCA], [https://pdbe.org/4en4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4en4 RCSB], [https://www.ebi.ac.uk/pdbsum/4en4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4en4 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/PDXK_HUMAN PDXK_HUMAN]] Required for synthesis of pyridoxal-5-phosphate from vitamin B6.
[https://www.uniprot.org/uniprot/PDXK_HUMAN PDXK_HUMAN] Required for synthesis of pyridoxal-5-phosphate from vitamin B6.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B(6), pyridoxal 5'-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B(6) is converted to PLP by PL kinase. PLP is the B(6) vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B(6), or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects.
 
Crystal structures of human pyridoxal kinase in complex with the neurotoxins, ginkgotoxin and theophylline: insights into pyridoxal kinase inhibition.,Gandhi AK, Desai JV, Ghatge MS, di Salvo ML, Di Biase S, Danso-Danquah R, Musayev FN, Contestabile R, Schirch V, Safo MK PLoS One. 2012;7(7):e40954. Epub 2012 Jul 18. PMID:22879864<ref>PMID:22879864</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4en4" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Pyridoxal kinase|Pyridoxal kinase]]
*[[Pyridoxal kinase|Pyridoxal kinase]]
== References ==
<references/>
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</StructureSection>
</StructureSection>

Latest revision as of 17:06, 13 March 2024

Crystal Structure of the Ternary Human PL Kinase-Ginkgotoxin-MgATP ComplexCrystal Structure of the Ternary Human PL Kinase-Ginkgotoxin-MgATP Complex

Structural highlights

4en4 is a 2 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 2.15Å
Ligands:, , , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PDXK_HUMAN Required for synthesis of pyridoxal-5-phosphate from vitamin B6.

See Also

4en4, resolution 2.15Å

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