View source for 9hha


==Crystal Structure of the Plasmodium vivax Bromodomain PvBDP1 in complex with RMM4==
<StructureSection load='9hha' size='340' side='right'caption='[[9hha]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hha]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_vivax Plasmodium vivax]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HHA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HHA 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IUX:3-methyl-1-[2-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydro-2~{H}-cyclohepta[c]pyrrol-4-one'>A1IUX</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=9hha FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hha OCA], [https://pdbe.org/9hha PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hha RCSB], [https://www.ebi.ac.uk/pdbsum/9hha PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hha ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A5KDW3_PLAVS A5KDW3_PLAVS] 
<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 9hha" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium vivax]]
[[Category: Amann M]]
[[Category: Einsle O]]
[[Category: Guenther S]]
[[Category: Huegle M]]