5k6a: Difference between revisions

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-'''Unreleased structure'''
-The entry 5k6a is ON HOLD
+==Trypanosoma brucei Pteridine reductase 1 (PTR1) in complex with compound 1==
+<StructureSection load='5k6a' size='340' side='right'caption='[[5k6a]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5k6a]] 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=5K6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K6A 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]] 1.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6QT:(2~{R})-2-(3-HYDROXYPHENYL)-6-OXIDANYL-2,3-DIHYDROCHROMEN-4-ONE'>6QT</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</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=5k6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6a OCA], [https://pdbe.org/5k6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k6a RCSB], [https://www.ebi.ac.uk/pdbsum/5k6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants.
-Authors: Landi, G., Pozzi, C., Di Pisa, F., Dello lacono, L., Mangani, S.
+Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.,Di Pisa F, Landi G, Dello Iacono L, Pozzi C, Borsari C, Ferrari S, Santucci M, Santarem N, Cordeiro-da-Silva A, Moraes CB, Alcantara LM, Fontana V, Freitas-Junior LH, Gul S, Kuzikov M, Behrens B, Pohner I, Wade RC, Costi MP, Mangani S Molecules. 2017 Mar 8;22(3). pii: E426. doi: 10.3390/molecules22030426. PMID:28282886<ref>PMID:28282886</ref>
-Description: Trypanosoma brucei Pteridine reductase 1 (PTR1) in complex with compound 1
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Landi, G]]
+<div class="pdbe-citations 5k6a" style="background-color:#fffaf0;"></div>
-[[Category: Dello Lacono, L]]
-[[Category: Pozzi, C]]
+==See Also==
-[[Category: Mangani, S]]
+*[[Pteridine reductase|Pteridine reductase]]
-[[Category: Di Pisa, F]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Trypanosoma brucei brucei]]
+[[Category: Dello lacono L]]
+[[Category: Di Pisa F]]
+[[Category: Landi G]]
+[[Category: Mangani S]]
+[[Category: Pozzi C]]