24kn

Crystal structure of the second bromodomain (BD2) of human BRD2 in complex with Nimesulide

spinqualitylabelsall models 24kn, resolution 1.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 24kn is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.69Å Ligands: NIM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BRD2_HUMAN May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly. Publication Abstract from PubMed The bromodomain and extra-terminal (BET) family of proteins, which regulate chromatin function, is an established potential drug target for treating major diseases such as cancer and inflammatory conditions. There is significant research focused on developing new BET inhibitors with innovative molecular structures to target and modulate the epigenetic mechanisms underlying major diseases, including cancer. Herein, we present the crystal structures of the second bromodomain (BD2) of hBRD2 in complex with the FDA-approved drugs, mefenamic acid (ID8) and nimesulide (NIM), and that of the first bromodomain (BD1) of hBRD4 in complex with nimesulide (NIM). Quantitative binding assays by surface plasmon resonance (SPR) confirmed the substantial binding of these drug molecules to the hBRD2 and hBRD4 bromodomains. Using these crystal structures, a series of ID8 and NIM derivatives with improved affinity relative to the parent compounds was designed and evaluated using SeeSAR (BioSolveIT GmbH). Moreover, molecular dynamics simulations were performed on the selected derivatives of ID8 and NIM against these bromodomains and confirmed the stability of these derivatives' binding throughout the simulations. We propose that the derivatives of the aforementioned parent molecules may be potential inhibitors of the function of hBRD2 and hBRD4. BET Bromodomain Targeting by NSAIDs: Structural, Biophysical, and Computational Insights.,Sridhar A, Kandhasami N, Mathur S, Krishnappa G, Thiyagarajan S, Padmanabhan B Proteins. 2026 Jul 15. doi: 10.1002/prot.70154. PMID:42458221 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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