3e0q
From Proteopedia
(Difference between revisions)
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:3e0q.png|left|200px]] | ||
| - | + | ==Crystal structure of Schistosoma mansoni purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor== | |
| + | <StructureSection load='3e0q' size='340' side='right'caption='[[3e0q]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3e0q]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E0Q FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=JFD:6-AMINO-5-BROMO-1,2,3,4-TETRAHYDROPYRIMIDINE-2,4-DIONE'>JFD</scene></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=3e0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e0q OCA], [https://pdbe.org/3e0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e0q RCSB], [https://www.ebi.ac.uk/pdbsum/3e0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e0q ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/Q9BMI9_SCHMA Q9BMI9_SCHMA] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate (By similarity).[PIRNR:PIRNR000477] | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e0/3e0q_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3e0q ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A novel inhibitor of Schistosoma PNP was identified using an "in silico" approach allied to enzyme inhibition assays. The compound has a monocyclic structure which has not been previously described for PNP inhibitors. The crystallographic structure of the complex was determined and used to elucidate the binding mode within the active site. Furthermore, the predicted pose was very similar to that determined crystallographically, validating the methodology. The compound Sm_VS1, despite its low molecular weight, possesses an IC(50) of 1.3 microM, surprisingly low when compared with purine analogues. This is presumably due to the formation of eight hydrogen bonds with key residues in the active site E203, N245 and T244. The results of this study highlight the importance of the use of multiple conformations for the target during virtual screening. Indeed the Sm_VS1 compound was only identified after flipping the N245 side chain. It is expected that the structure will be of use in the development of new highly active non-purine based compounds against the Schistosoma enzyme. | ||
| - | + | Crystal structure of Schistosoma purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor.,Pereira HM, Berdini V, Ferri MR, Cleasby A, Garratt RC Acta Trop. 2010 May;114(2):97-102. Epub 2010 Feb 1. PMID:20122887<ref>PMID:20122887</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 3e0q" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | [[ | + | *[[Purine nucleoside phosphorylase 3D structures|Purine nucleoside phosphorylase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Large Structures]] | ||
[[Category: Schistosoma mansoni]] | [[Category: Schistosoma mansoni]] | ||
| - | [[Category: Berdini | + | [[Category: Berdini V]] |
| - | [[Category: Cleasby | + | [[Category: Cleasby A]] |
| - | [[Category: Ferri | + | [[Category: Ferri MR]] |
| - | [[Category: Garratt | + | [[Category: Garratt RC]] |
| - | [[Category: Pereira | + | [[Category: Pereira HM]] |
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
Crystal structure of Schistosoma mansoni purine nucleoside phosphorylase complexed with a novel monocyclic inhibitor
| |||||||||||
