View source for 9hhd


==Crystal Structure of the Plasmodium falciparum Bromodomain PfBDP1 in complex with RMM2==
<StructureSection load='9hhd' size='340' side='right'caption='[[9hhd]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hhd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HHD 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]] 2.26&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IUZ:3-methyl-1-(2-methylphenyl)-5,6,7,8-tetrahydro-2~{H}-cyclohepta[c]pyrrol-4-one'>A1IUZ</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=9hhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hhd OCA], [https://pdbe.org/9hhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hhd RCSB], [https://www.ebi.ac.uk/pdbsum/9hhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hhd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IJ72_PLAF7 Q8IJ72_PLAF7] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The rise of drug resistances in malaria necessitates the exploration of novel therapeutic strategies. Targeting epigenetic pathways could open new, promising treatment avenues. In this study, we focus on the essential Bromodomain Protein 1 (PfBDP1) of the malaria pathogen Plasmodium falciparum. Utilizing the pan-selective bromodomain inhibitor MPM6, we identified a potent initial hit and subsequently developed it into a nanomolar binder. Through a combination of virtual docking, isothermal titration calorimetry, and X-ray crystallography, we elucidated the molecular interactions of the new inhibitors with the bromodomain (BRD) of the protein (PfBDP1-BRD). Our findings include the first co-crystallized inhibitors with the structures of PfBRD1-BRD as well as the bromodomain of the close homologous protein of Plasmodium vivax (PvBDP1-BRD). The structures provide new insights into their binding mechanisms. Further validation using conditional knockdown of PfBDP1 in P. falciparum demonstrated parasite sensitivity to the inhibitor, underscoring its potential in a targeted therapeutic approach against malaria.

A novel inhibitor against the Bromodomain Protein 1 of the malaria pathogen Plasmodium falciparum.,Amann M, Warstat R, Rechten KK, Theuer P, Schustereder M, Clavey S, Breit B, Einsle O, Hugle M, Petter M, Gunther S ChemMedChem. 2025 Mar 18:e202500024. doi: 10.1002/cmdc.202500024. PMID:40099623<ref>PMID:40099623</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hhd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Amann M]]
[[Category: Einsle O]]
[[Category: Guenther S]]
[[Category: Huegle M]]