4eoh: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal Structure of Human PL Kinase with bound Theophylline== | ==Crystal Structure of Human PL Kinase with bound Theophylline== | ||
<StructureSection load='4eoh' size='340' side='right' caption='[[4eoh]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4eoh' size='340' side='right' caption='[[4eoh]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4eoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4eoh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3kbi 3kbi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EOH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EOH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=TEP:THEOPHYLLINE'>TEP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>, <scene name='pdbligand=TEP:THEOPHYLLINE'>TEP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kbi|3kbi]], [[4en4|4en4]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3kbi|3kbi]], [[4en4|4en4]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDXK, C21orf124, C21orf97, PKH, PNK, PRED79 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PDXK, C21orf124, C21orf97, PKH, PNK, PRED79 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.35 2.7.1.35] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyridoxal_kinase Pyridoxal kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eoh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eoh RCSB], [http://www.ebi.ac.uk/pdbsum/4eoh PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eoh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eoh OCA], [http://pdbe.org/4eoh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eoh RCSB], [http://www.ebi.ac.uk/pdbsum/4eoh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eoh ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| Line 19: | Line 20: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4eoh" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 26: | Line 28: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Pyridoxal kinase]] | [[Category: Pyridoxal kinase]] | ||
[[Category: Gandhi, A K]] | [[Category: Gandhi, A K]] | ||
Revision as of 16:00, 4 August 2016
Crystal Structure of Human PL Kinase with bound TheophyllineCrystal Structure of Human PL Kinase with bound Theophylline
Structural highlights
Function[PDXK_HUMAN] Required for synthesis of pyridoxal-5-phosphate from vitamin B6. Publication Abstract from PubMedSeveral 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||