2Y1O: Dual-target Inhibitor of MurD and MurE Ligases: Design, Synthesis and Binding Mode Studies

Citation:
Abstract
MurD and MurE ligases, consecutive enzymes participating in the intracellular steps of bacterial peptidoglycan biosynthesis, are important targets for antibacterial drug discovery. We have designed, synthesized, and evaluated the first d-glutamic acid-containing dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus (IC50 values between 6.4 and 180 muM) possessing antibacterial activity against Gram-positive S. aureus and its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) values of 8 mug/mL. The inhibitor was also found to be noncytotoxic for human HepG2 cells at concentrations below 200 muM.
PDB ID: 2Y1ODownload
MMDB ID: 95997
PDB Deposition Date: 2010/12/9
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 1.49  Å
Source Organism:
Similar Structures:
Biological Unit for 2Y1O: monomeric; determined by author and by software (PISA)
Molecular Components in 2Y1O
Label Count Molecule
Protein (1 molecule)
1
Udp-n-acetylmuramoylalanine--d-glutamate Ligase(Gene symbol: murD)
Molecule annotation
Chemicals (9 molecules)
1
1
2
4
3
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.