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| | <StructureSection load='3zs7' size='340' side='right'caption='[[3zs7]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='3zs7' size='340' side='right'caption='[[3zs7]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3zs7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZS7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZS7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3zs7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei_TREU927 Trypanosoma brucei brucei TREU927]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZS7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2Å</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='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=PO4:PHOSPHATE+ION'>PO4</scene></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=3zs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zs7 OCA], [http://pdbe.org/3zs7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zs7 RCSB], [http://www.ebi.ac.uk/pdbsum/3zs7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zs7 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=3zs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zs7 OCA], [https://pdbe.org/3zs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zs7 RCSB], [https://www.ebi.ac.uk/pdbsum/3zs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zs7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O15927_9TRYP O15927_9TRYP] |
| | <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: Pyridoxal kinase]] | + | [[Category: Trypanosoma brucei brucei TREU927]] |
| - | [[Category: Alphey, M S]] | + | [[Category: Alphey MS]] |
| - | [[Category: Fairlamb, A H]] | + | [[Category: Fairlamb AH]] |
| - | [[Category: Jones, D C]] | + | [[Category: Jones DC]] |
| - | [[Category: Sleeping sickness]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
O15927_9TRYP
Publication Abstract from PubMed
Pyridoxal-5'-phosphate (vitamin B(6) ) is an essential cofactor for many important enzymatic reactions such as transamination and decarboxylation. African trypanosomes are unable to synthesise vitamin B(6) de novo and rely on uptake of B(6) vitamers such as pyridoxal and pyridoxamine from their hosts, which are subsequently phosphorylated by pyridoxal kinase (PdxK). A conditional null mutant of PdxK was generated in Trypanosoma brucei bloodstream forms showing that this enzyme is essential for growth of the parasite in vitro and for infectivity in mice. Activity of recombinant T. brucei PdxK was comparable to previously published work having a specific activity of 327 +/- 13 mU mg(-1) and a K(m) (app) with respect to pyridoxal of 29.6 +/- 3.9 microM. A coupled assay was developed demonstrating that the enzyme has equivalent catalytic efficiency with pyridoxal, pyridoxamine and pyridoxine, and that ginkgotoxin is an effective pseudo substrate. A high resolution structure of PdxK in complex with ATP revealed important structural differences with the human enzyme. These findings suggest that pyridoxal kinase is an essential and druggable target that could lead to much needed alternative treatments for this devastating disease.
Chemical, genetic and structural assessment of pyridoxal kinase as a drug target in the African trypanosome.,Jones DC, Alphey MS, Wyllie S, Fairlamb AH Mol Microbiol. 2012 Oct;86(1):51-64. doi: 10.1111/j.1365-2958.2012.08189.x. Epub , 2012 Aug 16. PMID:22857512[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jones DC, Alphey MS, Wyllie S, Fairlamb AH. Chemical, genetic and structural assessment of pyridoxal kinase as a drug target in the African trypanosome. Mol Microbiol. 2012 Oct;86(1):51-64. doi: 10.1111/j.1365-2958.2012.08189.x. Epub , 2012 Aug 16. PMID:22857512 doi:http://dx.doi.org/10.1111/j.1365-2958.2012.08189.x
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