9hhb

Crystal Structure of the Plasmodium vivax Bromodomain PvBDP1 in complex with RMM21

spinqualitylabelsall models 9hhb, resolution 2.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9hhb is a 1 chain structure with sequence from Plasmodium vivax. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.26Å Ligands: A1IUY, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A5KDW3_PLAVS 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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