4N96: E. Coli Sliding Clamp In Complex With 6-nitroindazole

Citation:
Abstract
The bacterial sliding clamp (SC), also known as the DNA polymerase III beta subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein-protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms showed minimum inhibitory concentrations in the range of 21-43 mug/mL against representative Gram-negative and Gram-positive bacteria species. The work demonstrates the utility of a fragment-based approach for identifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activity.
PDB ID: 4N96Download
MMDB ID: 114966
PDB Deposition Date: 2013/10/19
Updated in MMDB: 2013/11
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4N96: dimeric; determined by author and by software (PISA)
Molecular Components in 4N96
Label Count Molecule
Proteins (2 molecules)
2
DNA Polymerase III Subunit Beta(Gene symbol: dnaN)
Molecule annotation
Chemicals (10 molecules)
1
1
2
3
3
4
4
2
* Click molecule labels to explore molecular sequence information.

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