View source for 9hup


==Trypanosoma brucei PTR1 (TbPTR1) in complex with inhibitor F194==
<StructureSection load='9hup' size='340' side='right'caption='[[9hup]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hup]] 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=9HUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HUP 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]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IXO:2-azanyl-~{N}-[2-(3,4-dichlorophenyl)ethyl]-1,3-benzothiazole-6-carboxamide'>A1IXO</scene>, <scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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=9hup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hup OCA], [https://pdbe.org/9hup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hup RCSB], [https://www.ebi.ac.uk/pdbsum/9hup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hup ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pteridine reductase 1 (PTR1) is a folate pathway enzyme essential for pathogenic trypanosomatids and a promising drug target for diseases such as sleeping sickness and leishmaniasis. Previous studies have shown that the 2-aminobenzothiazole moiety targets the PTR1 biopterin pocket, while 3,4-dichlorophenyl-containing compounds, such as I bind a different region of the Trypanosoma brucei PTR1 (TbPTR1) pocket. This study combines both moieties via various linkers, creating two compound series screened in silico against TbPTR1 and Leishmania major PTR1 (LmPTR1). In the first series, five compounds were synthesized, and 1a and 1b emerged as potent TbPTR1 inhibitors, with 1b also being active against LmPTR1 and moderately effective against Leishmania infantum. Furthermore, structure-activity relationship analysis, supported by quantum calculations and crystallography, revealed meta-halogenation to be more favorable than para, although single halogenation reduced antiparasite effects. Our fragment hybridization approach led to less toxic, more effective compounds than I.

Design of 2-Aminobenzothiazole Derivatives Targeting Trypanosomatid PTR1 by a Multidisciplinary Fragment Hybridization Approach.,Panecka-Hofman J, Linciano P, Pohner I, Dyguda-Kazimierowicz E, Jedwabny W, Landi G, Santarem N, Witt G, Ellinger B, Kuzikov M, Luciani R, Ferrari S, Aiello D, Mangani S, Pozzi C, Cordeiro-da-Silva A, Gul S, Costi MP, Wade RC J Med Chem. 2025 Oct 9;68(19):20595-20618. doi: 10.1021/acs.jmedchem.5c01799. , Epub 2025 Sep 30. PMID:41026998<ref>PMID:41026998</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hup" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei brucei]]
[[Category: Landi G]]
[[Category: Mangani S]]
[[Category: Pozzi C]]