2020
DOI: 10.1002/cmdc.201900721
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Covalent Complex of DNA and Bacterial Topoisomerase: Implications in Antibacterial Drug Development

Abstract: A topoisomerase‐DNA transient covalent complex can be a druggable target for novel topoisomerase poison inhibitors that represent a new class of antibacterial or anticancer drugs. Herein, we have investigated molecular features of the functionally important Escherichia coli topoisomerase I (EctopoI)‐DNA covalent complex (EctopoIcc) for molecular simulations, which is very useful in the development of new antibacterial drugs. To demonstrate the usefulness of our approach, we used a model small molecule (SM), NS… Show more

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Cited by 13 publications
(12 citation statements)
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“…In silico virtual screening employing docking and molecular dynamics (MD) simulations can be used first to identify potential inhibitors from compound libraries, followed by biochemical assays on a small number of in silico hits with the highest predicted binding affinity to confirm the interaction and assess the topoisomerase inhibition and antimicrobial activity. This approach has been applied to identify inhibitors for E. coli and M. tuberculosis topoisomerase I using either crystal structures or target structures generated by computational modeling [ 94 , 95 , 96 , 97 , 98 ].…”
Section: Screening Approachesmentioning
confidence: 99%
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“…In silico virtual screening employing docking and molecular dynamics (MD) simulations can be used first to identify potential inhibitors from compound libraries, followed by biochemical assays on a small number of in silico hits with the highest predicted binding affinity to confirm the interaction and assess the topoisomerase inhibition and antimicrobial activity. This approach has been applied to identify inhibitors for E. coli and M. tuberculosis topoisomerase I using either crystal structures or target structures generated by computational modeling [ 94 , 95 , 96 , 97 , 98 ].…”
Section: Screening Approachesmentioning
confidence: 99%
“…To identify candidates for bacterial topoisomerase I poison inhibitors, stabilization of the covalent intermediate formed after DNA cleavage was targeted for in silico screening [ 94 ]. The C-terminal domains of E. coli topoisomerase I (from full length structure PDB 4RUL) were connected to the 67 kDa N-terminal domains in covalent complex with cleaved DNA (PDB 3PX7) based on alignments of the two structures.…”
Section: Recent Attempts To Discover Novel Bacterial Topoisomerasementioning
confidence: 99%
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“…Besides, conventional SPR on the continuous metal surface, there are other biosensing applications based on nanoparticles as sensors that include but not limited to OpenSPR (Nicoya) and SoPRano (BMG LABTECH) using localized surface plasmon resonance (LSPR) technology [ 4 ] as well as INB-D200 (INSTANT NanoBiosensors) using fiber optic particle plasmon resonance (FOPPR) [ 5 ] utilizing SPR effects. The SPR technique is very useful in SM binding [ 6 , 7 ], hit validation [ 7 ], and lead identification [ 8 ] in drug discovery via the detection of direct molecular interactions [ 9 ]. One of the two interacting partners is immobilized on the metal chip surface (ligand) whereas the other binding partner in solution (analyte) is flown over the ligand-immobilized surface [ 10 ].…”
Section: Introductionmentioning
confidence: 99%