2wd8: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204== | ==PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204== | ||
<StructureSection load='2wd8' size='340' side='right' caption='[[2wd8]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='2wd8' size='340' side='right'caption='[[2wd8]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wd8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WD8 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2wd8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WD8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WD8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=VGF:1-(3,4-DICHLOROBENZYL)-7-PHENYL-1H-BENZIMIDAZOL-2-AMINE'>VGF</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=VGF:1-(3,4-DICHLOROBENZYL)-7-PHENYL-1H-BENZIMIDAZOL-2-AMINE'>VGF</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vz0|2vz0]], [[2c7v|2c7v]], [[2wd7|2wd7]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vz0|2vz0]], [[2c7v|2c7v]], [[2wd7|2wd7]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pteridine_reductase Pteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.33 1.5.1.33] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pteridine_reductase Pteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.33 1.5.1.33] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wd8 OCA], [http://pdbe.org/2wd8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wd8 RCSB], [http://www.ebi.ac.uk/pdbsum/2wd8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wd8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
| Line 35: | Line 35: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Pteridine reductase]] | [[Category: Pteridine reductase]] | ||
[[Category: Trybb]] | [[Category: Trybb]] | ||
Revision as of 11:36, 1 July 2020
PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204
Structural highlights
Evolutionary 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
|
| ||||||||||||||||||||