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==PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00066750== | ==PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00066750== | ||
<StructureSection load='2wd7' size='340' side='right' caption='[[2wd7]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2wd7' size='340' side='right'caption='[[2wd7]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wd7]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2wd7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WD7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WD7 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[ | </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><td class="sblockLbl"><b>[[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=VGD:6-CHLORO-1H-BENZIMIDAZOL-2-AMINE'>VGD</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=2wd7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wd7 OCA], [https://pdbe.org/2wd7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wd7 RCSB], [https://www.ebi.ac.uk/pdbsum/2wd7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wd7 ProSAT]</span></td></tr> | |||
</table> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | == Function == | ||
<table> | [https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB] | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/2wd7_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/2wd7_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=2wd7 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 27: | Line 28: | ||
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 2wd7" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 34: | Line 36: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Trypanosoma brucei brucei]] | [[Category: Trypanosoma brucei brucei]] | ||
[[Category: Brenk | [[Category: Brenk R]] | ||
[[Category: Robinson | [[Category: Robinson DA]] | ||
[[Category: Spinks | [[Category: Spinks D]] | ||
[[Category: Wyatt | [[Category: Wyatt PG]] | ||
Latest revision as of 18:52, 13 December 2023
PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00066750PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00066750
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe enzyme pteridine reductase 1 (PTR1) is a potential target for new compounds to treat human African trypanosomiasis. A virtual screening campaign for fragments inhibiting PTR1 was carried out. Two novel chemical series were identified containing aminobenzothiazole and aminobenzimidazole scaffolds, respectively. One of the hits (2-amino-6-chloro-benzimidazole) was subjected to crystal structure analysis and a high resolution crystal structure in complex with PTR1 was obtained, confirming the predicted binding mode. However, the crystal structures of two analogues (2-amino-benzimidazole and 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole) in complex with PTR1 revealed two alternative binding modes. In these complexes, previously unobserved protein movements and water-mediated protein-ligand contacts occurred, which prohibited a correct prediction of the binding modes. On the basis of the alternative binding mode of 1-(3,4-dichloro-benzyl)-2-amino-benzimidazole, derivatives were designed and selective PTR1 inhibitors with low nanomolar potency and favorable physicochemical properties were obtained. One Scaffold, Three Binding Modes: Novel and Selective Pteridine Reductase 1 Inhibitors Derived from Fragment Hits Discovered by Virtual Screening.,Mpamhanga CP, Spinks D, Tulloch LB, Shanks EJ, Robinson DA, Collie IT, Fairlamb AH, Wyatt PG, Frearson JA, Hunter WN, Gilbert IH, Brenk R J Med Chem. 2009 Jun 15. PMID:19527033[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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