7P2N
E.coli GyrB24 with inhibitor LSJ38 (EBL2684)
Summary for 7P2N
| Entry DOI | 10.2210/pdb7p2n/pdb |
| Descriptor | DNA gyrase subunit B, PHOSPHATE ION, 2-[[3,4-bis(chloranyl)-5-methyl-1H-pyrrol-2-yl]carbonylamino]-5-oxidanyl-1,3-benzothiazole-6-carboxylic acid, ... (4 entities in total) |
| Functional Keywords | gyrase, inhibitor, e.coli, complex, dna binding protein |
| Biological source | Escherichia coli (strain K12) |
| Total number of polymer chains | 1 |
| Total formula weight | 24672.36 |
| Authors | Stevenson, C.E.M.,Lawson, D.M.,Maxwell, A.M.,Henderson, S.R.,Kikelj, D.,Zega, A.,Zidar, N.,Ilas, J.,Tomasic, T.,Masic, L.P. (deposition date: 2021-07-06, release date: 2022-07-20, Last modification date: 2024-01-31) |
| Primary citation | Sterle, M.,Durcik, M.,Stevenson, C.E.M.,Henderson, S.R.,Szili, P.E.,Czikkely, M.,Lawson, D.M.,Maxwell, A.,Cahard, D.,Kikelj, D.,Zidar, N.,Pal, C.,Masic, L.P.,Ilas, J.,Tomasic, T.,Cotman, A.E.,Zega, A. Exploring the 5-Substituted 2-Aminobenzothiazole-Based DNA Gyrase B Inhibitors Active against ESKAPE Pathogens. Acs Omega, 8:24387-24395, 2023 Cited by PubMed Abstract: We present a new series of 2-aminobenzothiazole-based DNA gyrase B inhibitors with promising activity against ESKAPE bacterial pathogens. Based on the binding information extracted from the cocrystal structure of DNA gyrase B inhibitor , in complex with GyrB24, we expanded the chemical space of the benzothiazole-based series to the C5 position of the benzothiazole ring. In particular, compound showed low nanomolar inhibition of DNA gyrase (IC < 10 nM) and broad-spectrum antibacterial activity against pathogens belonging to the ESKAPE group, with the minimum inhibitory concentration < 0.03 μg/mL for most Gram-positive strains and 4-16 μg/mL against Gram-negative , , and . To understand the binding mode of the synthesized inhibitors, a combination of docking calculations, molecular dynamics (MD) simulations, and MD-derived structure-based pharmacophore modeling was performed. The computational analysis has revealed that the substitution at position C5 can be used to modify the physicochemical properties and antibacterial spectrum and enhance the inhibitory potency of the compounds. Additionally, a discussion of challenges associated with the synthesis of 5-substituted 2-aminobenzothiazoles is presented. PubMed: 37457471DOI: 10.1021/acsomega.3c01930 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.16 Å) |
Structure validation
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