9FOY

Ternary complex of a Mycobacterium tuberculosis DNA gyrase core fusion with DNA and the inhibitor AMK32b

This is a non-PDB format compatible entry.

Summary for 9FOY

• Entry DOI: 10.2210/pdb9foy/pdb
• Descriptor: DNA gyrase subunit B,DNA gyrase subunit A, DNA (5'-D(*AP*GP*CP*CP*GP*TP*AP*G)-3'), DNA (5'-D(P*GP*TP*AP*CP*CP*TP*AP*CP*GP*GP*CP*T)-3'), ... (5 entities in total)
• Functional Keywords: type iia topoisomerase, antibacterial, inhibitor, isomerase, fusion protein
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 6
• Total formula weight: 181960.52

Authors

Kokot, M.,Hrast, M.,Feng, L.,Mitchenall, L.A.,Lawson, D.M.,Maxwell, A.,Minovski, N.,Anderluh, M. (deposition date: 2024-06-12, release date: 2024-08-07, Last modification date: 2025-02-19)

Primary citation

Kokot, M.,Hrast Rambaher, M.,Feng, L.,Mitchenall, L.A.,Lawson, D.M.,Maxwell, A.,Parish, T.,Minovski, N.,Anderluh, M.
Structural Aspects of Mycobacterium tuberculosis DNA Gyrase Targeted by Novel Bacterial Topoisomerase Inhibitors.
Acs Med.Chem.Lett., 15:2164-2170, 2024

PubMed Abstract: In this Letter, we present a small series of novel bacterial topoisomerase inhibitors (NTBIs) that exhibit both potent inhibition of DNA gyrase and potent antimycobacterial activity. The disclosed crystal structure of DNA gyrase in complex with DNA and compound from this NBTI series reveals the binding mode of an NBTI in the GyrA binding pocket and confirms the presence and importance of halogen bonding for the excellent on-target potency. In addition, we have shown that compound is a promising DNA gyrase inhibitor, with an IC for gyrase of 0.096 μM, and it has potent activity against , with an IC of 0.165 μM.

PubMed: 39691510
DOI: 10.1021/acsmedchemlett.4c00447

Experimental method

X-RAY DIFFRACTION (2.8 Å)