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1w0c
From Proteopedia
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| - | {{STRUCTURE_1w0c| PDB=1w0c | SCENE= }} | ||
| - | ===INHIBITION OF LEISHMANIA MAJOR PTERIDINE REDUCTASE (PTR1) BY 2,4,6-TRIAMINOQUINAZOLINE; STRUCTURE OF THE NADP TERNARY COMPLEX.=== | ||
| - | {{ABSTRACT_PUBMED_15388924}} | ||
| - | == | + | ==Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.== |
| - | [[1w0c]] is a 8 chain structure with sequence from [ | + | <StructureSection load='1w0c' size='340' side='right'caption='[[1w0c]], [[Resolution|resolution]] 2.60Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1w0c]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0C 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TAQ:2,4,6-TRIAMINOQUINAZOLINE'>TAQ</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=1w0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0c OCA], [https://pdbe.org/1w0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0c RCSB], [https://www.ebi.ac.uk/pdbsum/1w0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0c ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PTR1_LEIMA PTR1_LEIMA] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).<ref>PMID:7972081</ref> | ||
| + | == 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/w0/1w0c_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=1w0c ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors. | ||
| + | |||
| + | Inhibition of Leishmania major pteridine reductase by 2,4,6-triaminoquinazoline: structure of the NADPH ternary complex.,McLuskey K, Gibellini F, Carvalho P, Avery MA, Hunter WN Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1780-5. Epub 2004, Sep 23. PMID:15388924<ref>PMID:15388924</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 1w0c" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Pteridine reductase|Pteridine reductase]] | *[[Pteridine reductase|Pteridine reductase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Leishmania major]] | [[Category: Leishmania major]] | ||
| - | + | [[Category: Avery M]] | |
| - | [[Category: Avery | + | [[Category: Carvalho P]] |
| - | [[Category: Carvalho | + | [[Category: Gibellini F]] |
| - | [[Category: Gibellini | + | [[Category: Hunter W]] |
| - | [[Category: Hunter | + | [[Category: Mcluskey K]] |
| - | [[Category: Mcluskey | + | |
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Current revision
Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.
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