9hhc: Difference between revisions
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New page: '''Unreleased structure''' The entry 9hhc is ON HOLD Authors: Amann, M., Huegle, M., Einsle, O., Guenther, S. Description: Crystal Structure of the Plasmodium falciparum Bromodomain Pf... |
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==Crystal Structure of the Plasmodium falciparum Bromodomain PfBDP1 in complex with MPM2== | |||
<StructureSection load='9hhc' size='340' side='right'caption='[[9hhc]], [[Resolution|resolution]] 1.56Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9hhc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HHC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HHC 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]] 1.56Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=I5K:1-(3-aminophenyl)-3-methyl-5,6,7,8-tetrahydro-2~{H}-cyclohepta[c]pyrrol-4-one'>I5K</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=9hhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hhc OCA], [https://pdbe.org/9hhc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hhc RCSB], [https://www.ebi.ac.uk/pdbsum/9hhc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hhc 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9hhc" style="background-color:#fffaf0;"></div> | ||
[[Category: Einsle | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Amann M]] | |||
[[Category: Einsle O]] | |||
[[Category: Guenther S]] | |||
[[Category: Huegle M]] | |||
Latest revision as of 09:23, 2 April 2025
Crystal Structure of the Plasmodium falciparum Bromodomain PfBDP1 in complex with MPM2
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