3wxk: Difference between revisions
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==Crystal structure of trypanosoma brucei gambiense glycerol kinase in complex with glycerol== | ==Crystal structure of trypanosoma brucei gambiense glycerol kinase in complex with glycerol== | ||
<StructureSection load='3wxk' size='340' side='right' caption='[[3wxk]], [[Resolution|resolution]] 2.37Å' scene=''> | <StructureSection load='3wxk' size='340' side='right'caption='[[3wxk]], [[Resolution|resolution]] 2.37Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3wxk]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3wxk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trybg Trybg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WXK FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEZ:HEXANE-1,6-DIOL'>HEZ</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wxi|3wxi]], [[3wxj|3wxj]], [[3wxl|3wxl]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wxi|3wxi]], [[3wxj|3wxj]], [[3wxl|3wxl]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gk ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gk ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=31285 TRYBG])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glycerol_kinase Glycerol kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.30 2.7.1.30] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wxk OCA], [https://pdbe.org/3wxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wxk RCSB], [https://www.ebi.ac.uk/pdbsum/3wxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wxk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Glycerol kinase]] | [[Category: Glycerol kinase]] | ||
[[Category: Large Structures]] | |||
[[Category: Trybg]] | [[Category: Trybg]] | ||
[[Category: Aoki, T]] | [[Category: Aoki, T]] | ||
Revision as of 08:34, 10 August 2022
Crystal structure of trypanosoma brucei gambiense glycerol kinase in complex with glycerolCrystal structure of trypanosoma brucei gambiense glycerol kinase in complex with glycerol
Structural highlights
Publication Abstract from PubMedThe glycerol kinase (GK) of African human trypanosomes is compartmentalized in their glycosomes. Unlike the host GK, which under physiological conditions catalyzes only the forward reaction (ATP-dependent glycerol phosphorylation), trypanosome GK can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, GK is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure-based catalytic differences also contribute. To investigate this lack of information, the X-ray crystal structure of this protein was determined up to 1.90 A resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure-guided mutagenesis suggests that the trypanosome GK is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non-conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome GK-specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s). Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase.,Balogun EO, Inaoka DK, Shiba T, Kido Y, Tsuge C, Nara T, Aoki T, Honma T, Tanaka A, Inoue M, Matsuoka S, Michels PA, Kita K, Harada S Mol Microbiol. 2014 Dec;94(6):1315-29. doi: 10.1111/mmi.12831. Epub 2014 Nov 4. PMID:25315291[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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