4EMV: Crystal Structure Of A Topoisomerase Atp Inhibitor

Citation:
Abstract
We present the discovery and optimization of a novel series of bacterial topoisomerase inhibitors. Starting from a virtual screening hit, activity was optimized through a combination of structure-based design and physical property optimization. Synthesis of fewer than a dozen compounds was required to achieve inhibition of the growth of methicillin-resistant Staphyloccus aureus (MRSA) at compound concentrations of 1.56muM. These compounds simultaneously inhibit DNA gyrase and Topoisomerase IV at similar nanomolar concentrations, reducing the likelihood of the spontaneous occurrence of target-based mutations resulting in antibiotic resistance, an increasing threat in the treatment of serious infections.
PDB ID: 4EMVDownload
MMDB ID: 101669
PDB Deposition Date: 2012/4/12
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4EMV: monomeric; determined by author and by software (PISA)
Molecular Components in 4EMV
Label Count Molecule
Protein (1 molecule)
1
DNA Topoisomerase IV, B Subunit
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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