2wd8: Difference between revisions

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-[[Image:2wd8.png|left|200px]]
-<!--
+==PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204==
-The line below this paragraph, containing "STRUCTURE_2wd8", creates the "Structure Box" on the page.
+<StructureSection load='2wd8' size='340' side='right'caption='[[2wd8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2wd8]] 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=2WD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WD8 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</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>
-{{STRUCTURE_2wd8|  PDB=2wd8  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wd8 OCA], [https://pdbe.org/2wd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wd8 RCSB], [https://www.ebi.ac.uk/pdbsum/2wd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wd8 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB]
+== 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/wd/2wd8_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=2wd8 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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.
-===PTERIDINE REDUCTASE 1 (PTR1) FROM TRYPANOSOMA BRUCEI IN COMPLEX WITH NADP AND DDD00071204===
+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<ref>PMID:19527033</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2wd8" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_19527033}}, adds the Publication Abstract to the page
+*[[Pteridine reductase|Pteridine reductase]]
-(as it appears on PubMed at http://www.pubmed.gov), where 19527033 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19527033}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-[[2wd8]] is a 4 chain structure with sequence from [http://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=2WD8 OCA].
-==Reference==
-<ref group="xtra">PMID:019527033</ref><ref group="xtra">PMID:016968221</ref><references group="xtra"/>
-[[Category: Pteridine reductase]]
 [[Category: Trypanosoma brucei brucei]]
-[[Category: Brenk, R.]]
+[[Category: Brenk R]]
-[[Category: Robinson, D A.]]
+[[Category: Robinson DA]]
-[[Category: Spinks, D.]]
+[[Category: Spinks D]]
-[[Category: Wyatt, P G.]]
+[[Category: Wyatt PG]]
-[[Category: Drug discovery]]
-[[Category: Methotrexate resistance]]
-[[Category: Oxidoreductase]]
-[[Category: Pteridine reductase]]
-[[Category: Short-chain dehydrogenase/reductase]]
-[[Category: Trypanosomatid]]