5ipf: Difference between revisions
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==Crystal structure of Hypoxanthine-guanine phosphoribosyltransferase from Schistosoma mansoni in complex with IMP== | ==Crystal structure of Hypoxanthine-guanine phosphoribosyltransferase from Schistosoma mansoni in complex with IMP== | ||
<StructureSection load='5ipf' size='340' side='right' caption='[[5ipf]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='5ipf' size='340' side='right'caption='[[5ipf]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ipf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IPF FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ipf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IPF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IMP:INOSINIC+ACID'>IMP</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HGPRT, Smp_103560 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6183 Blood fluke])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </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=5ipf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ipf OCA], [http://pdbe.org/5ipf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ipf RCSB], [http://www.ebi.ac.uk/pdbsum/5ipf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ipf ProSAT]</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=5ipf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ipf OCA], [http://pdbe.org/5ipf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ipf RCSB], [http://www.ebi.ac.uk/pdbsum/5ipf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ipf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Schistosoma mansoni, the parasite responsible for schistosomiasis, lacks the "de novo" purine biosynthetic pathway and depends entirely on the purine salvage pathway for the supply of purines. Numerous reports of praziquantel resistance have been described, as well as stimulated efforts to develop new drugs against schistosomiasis. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine salvage pathway. Here, we describe a crystallographic structure of the S. mansoni HPGRT-1 (SmHGPRT), complexed with IMP at a resolution of 2.8 A. Four substitutions were identified in the region of the active site between SmHGPRT-1 and human HGPRT. We also present data from RNA-Seq and WISH, suggesting that some isoforms of HGPRT might be involved in the process related to sexual maturation and reproduction in worms; furthermore, its enzymatic assays show that the isoform SmHGPRT-3 does not present the same catalytic efficiency as other isoforms. Finally, although other studies have previously suggested this enzyme as a potential antischistosomal chemotherapy target, the kinetics parameters reveal the impossibility to use SmHGPRT as an efficient chemotherapeutic target. | |||
In vitro and in vivo characterization of the multiple isoforms of Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferases.,Romanello L, Zeraik AE, de Freitas Fernandes A, Torini JR, Bird LE, Nettleship JE, Rada H, Reddivari Y, Owens RJ, Serrao VHB, DeMarco R, Brandao-Neto J, Pereira HD Mol Biochem Parasitol. 2019 Feb 14;229:24-34. doi:, 10.1016/j.molbiopara.2019.02.005. PMID:30772423<ref>PMID:30772423</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5ipf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Blood fluke]] | |||
[[Category: Hypoxanthine phosphoribosyltransferase]] | [[Category: Hypoxanthine phosphoribosyltransferase]] | ||
[[Category: Large Structures]] | |||
[[Category: Bird, L E]] | [[Category: Bird, L E]] | ||
[[Category: Brandao-Neto, J]] | [[Category: Brandao-Neto, J]] | ||