8JFF
Crystal structure of Catabolite repressor acivator from E. coli in complex with HEPES
Summary for 8JFF
| Entry DOI | 10.2210/pdb8jff/pdb |
| Descriptor | Catabolite repressor/activator, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID (3 entities in total) |
| Functional Keywords | cra, hepes, dna binding protein, gene regulation |
| Biological source | Escherichia coli 536 |
| Total number of polymer chains | 2 |
| Total formula weight | 76579.27 |
| Authors | |
| Primary citation | Neetu, N.,Mahto, J.K.,Sharma, M.,Katiki, M.,Dhaka, P.,Roy, P.,Tomar, S.,Narayan, A.,Yernool, D.,Kumar, P. Sulisobenzone is a potent inhibitor of the global transcription factor Cra. J.Struct.Biol., 215:108034-108034, 2023 Cited by PubMed Abstract: 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 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. PubMed: 37805153DOI: 10.1016/j.jsb.2023.108034 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.89 Å) |
Structure validation
Download full validation report
