3pf3: Difference between revisions
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==Crystal structure of a mutant (C202A) of Triosephosphate isomerase from Giardia lamblia derivatized with MMTS== | ==Crystal structure of a mutant (C202A) of Triosephosphate isomerase from Giardia lamblia derivatized with MMTS== | ||
<StructureSection load='3pf3' size='340' side='right' caption='[[3pf3]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='3pf3' size='340' side='right' caption='[[3pf3]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3pf3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3pf3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Giain Giain]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PF3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PF3 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCH:S-METHYL-THIO-CYSTEINE'>SCH</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dp3|2dp3]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2dp3|2dp3]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLTIM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5741 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLTIM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5741 GIAIN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Triose-phosphate_isomerase Triose-phosphate isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.1.1 5.3.1.1] </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=3pf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pf3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pf3 RCSB], [http://www.ebi.ac.uk/pdbsum/3pf3 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=3pf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pf3 OCA], [http://pdbe.org/3pf3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pf3 RCSB], [http://www.ebi.ac.uk/pdbsum/3pf3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pf3 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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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 3pf3" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Giain]] | ||
[[Category: Triose-phosphate isomerase]] | [[Category: Triose-phosphate isomerase]] | ||
[[Category: Enriquez-Flores, S]] | [[Category: Enriquez-Flores, S]] | ||
Revision as of 23:13, 5 August 2016
Crystal structure of a mutant (C202A) of Triosephosphate isomerase from Giardia lamblia derivatized with MMTSCrystal structure of a mutant (C202A) of Triosephosphate isomerase from Giardia lamblia derivatized with MMTS
Structural highlights
Publication Abstract from PubMedGiardiasis, the most prevalent intestinal parasitosis in humans, is caused by Giardia lamblia. Current drug therapies have adverse effects on the host, and resistant strains against these drugs have been reported, demonstrating an urgent need to design more specific antigiardiasic drugs. ATP production in G. lamblia depends mainly on glycolysis; therefore, all enzymes of this pathway have been proposed as potential drug targets. We previously demonstrated that the glycolytic enzyme triosephosphate isomerase from G. lamblia (GlTIM), could be completely inactivated by low micromolar concentrations of thiol-reactive compounds, whereas, in the same conditions, the activity of human TIM (HuTIM) was almost unaltered. We found that the chemical modification (derivatization) of at least one Cys, of the five Cys residues per monomer in GlTIM, causes this inactivation. In this study, structural and functional studies were performed to describe the molecular mechanism of GlTIM inactivation by thiol-reactive compounds. We found that the Cys222 derivatization is responsible for GlTIM inactivation; this information is relevant because HuTIM has a Cys residue in an equivalent position (Cys217). GlTIM inactivation is associated with a decrease in ligand affinity, which affects the entropic component of ligand binding. In summary, this work describes a mechanism of inactivation that has not been previously reported for TIMs from other parasites and furthermore, we show that the difference in reactivity between the Cys222 in GlTIM and the Cys217 in HuTIM, indicates that the surrounding environment of each Cys residue has unique structural differences that can be exploited to design specific antigiardiasic drugs. Proteins 2011;. (c) 2011 Wiley-Liss, Inc. Determining the molecular mechanism of inactivation by chemical modification of triosephosphate isomerase from the human parasite Giardia lamblia: A study for antiparasitic drug design.,Enriquez-Flores S, Rodriguez-Romero A, Hernandez-Alcantara G, Oria-Hernandez J, Gutierrez-Castrellon P, Perez-Hernandez G, Mora Ide L, Castillo-Villanueva A, Garcia-Torres I, Mendez ST, Gomez-Manzo S, Torres-Arroyo A, Lopez-Velazquez G, Reyes-Vivas H Proteins. 2011 Sep;79(9):2711-24. doi: 10.1002/prot.23100. Epub 2011 Jul, 22. PMID:21786322[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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