6qqm: Difference between revisions

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 <StructureSection load='6qqm' size='340' side='right'caption='[[6qqm]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6qqm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QQM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QQM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6qqm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QQM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QQM 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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Smp_168730 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6183 Blood fluke])</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=6qqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qqm OCA], [http://pdbe.org/6qqm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qqm RCSB], [http://www.ebi.ac.uk/pdbsum/6qqm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qqm ProSAT]</span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </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=6qqm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qqm OCA], [https://pdbe.org/6qqm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qqm RCSB], [https://www.ebi.ac.uk/pdbsum/6qqm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qqm ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Here we identify an alpha-carbonic anhydrase (SmCA) that is expressed at the schistosome surface as determined by activity assays and immunofluorescence/immunogold localization. Suppressing SmCA expression by RNAi significantly impairs the ability of larval parasites to infect mice, validating SmCA as a rational drug target. Purified, recombinant SmCA possesses extremely rapid CO2 hydration kinetics (kcat: 1.2 x 10(6) s(-1); kcat/Km: 1.3 x 10(8) M(-1)s(-1)). The enzyme's crystal structure was determined at 1.75 A resolution and a collection of sulfonamides and anions were tested for their ability to impede rSmCA action. Several compounds (phenylarsonic acid, phenylbaronic acid, sulfamide) exhibited favorable Kis for SmCA versus two human isoforms. Such selective rSmCA inhibitors could form the basis of urgently needed new drugs that block essential schistosome metabolism, blunt parasite virulence and debilitate these important global pathogens.
+Tegumental carbonic anhydrase from the worm Schistosoma mansoni (SmCA) is considered a new anti-parasitic target because suppressing its expression interferes with schistosome metabolism and virulence. Here, we present the inhibition profiles of selenoureido compounds on recombinant SmCA and resolution of the first X-ray crystal structures of SmCA in adduct with a selection of such inhibitors. The key molecular features of such compounds in adduct with SmCA were obtained and compared to the human isoform hCA II, in order to understand the main structural factors responsible for enzymatic affinity and selectivity. Compounds that more specifically inhibited the schistosome versus human enzymes were identified. The results expand current knowledge in the field and pave the way for the development of more potent antiparasitic agents in the near future.
-Crystal structure and chemical inhibition of essential schistosome host-interactive virulence factor carbonic anhydrase SmCA.,Da'dara AA, Angeli A, Ferraroni M, Supuran CT, Skelly PJ Commun Biol. 2019 Sep 5;2:333. doi: 10.1038/s42003-019-0578-0. eCollection 2019. PMID:31508507<ref>PMID:31508507</ref>
+Structural Insights into Schistosoma mansoni Carbonic Anhydrase (SmCA) Inhibition by Selenoureido-Substituted Benzenesulfonamides.,Angeli A, Ferraroni M, Da'dara AA, Selleri S, Pinteala M, Carta F, Skelly PJ, Supuran CT J Med Chem. 2021 Jul 22;64(14):10418-10428. doi: 10.1021/acs.jmedchem.1c00840., Epub 2021 Jul 7. PMID:34232641<ref>PMID:34232641</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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 __TOC__
 </StructureSection>
+[[Category: Blood fluke]]
 [[Category: Carbonate dehydratase]]
 [[Category: Large Structures]]