8jfv | pdb_00008jfv

Crystal structure of Catabolite repressor acivator from E. coli in complex with sulisobenzone

spinqualitylabelsall models 8jfv, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jfv is a 2 chain structure with sequence from Escherichia coli 536. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.05Å Ligands: EDO, EPE, I4Y, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Transcription is carried out by the RNA polymerase and is regulated through a series of interactions with transcription factors. Catabolite activator repressor (Cra), a LacI family transcription factor regulates the virulence gene expression in Enterohaemorrhagic Escherichia coli (EHEC) and thus is a promising drug target for the discovery of antivirulence molecules. Here, we report the crystal structure of the effector molecule binding domain of Cra from E. coli (EcCra) in complex with HEPES molecule. Based on the EcCra-HEPES complex structure, ligand screening was performed that identified sulisobenzone as an potential inhibitor of EcCra. The electrophoretic mobility shift assay (EMSA) and in vitro transcription assay validated the sulisobenzone binding to EcCra. Moreover, the isothermal titration calorimetry (ITC) experiments demonstrated a 40-fold higher binding affinity of sulisobenzone (K(D) 360 nM) compared to the HEPES molecule. Finally, the sulisobenzone bound EcCra complex crystal structure was determined to elucidate the binding mechanism of sulisobenzone to the effector binding pocket of EcCra. Together, this study suggests that sulisobenzone may be a promising candidate that can be studied and developed as an effective antivirulence agent against EHEC. Sulisobenzone is a potent inhibitor of the global transcription factor Cra.,Neetu N, Mahto JK, Sharma M, Katiki M, Dhaka P, Roy P, Tomar S, Narayan A, Yernool D, Kumar P J Struct Biol. 2023 Dec;215(4):108034. doi: 10.1016/j.jsb.2023.108034. Epub 2023 , Oct 5. PMID:37805153 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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