2Y1O

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

Summary for 2Y1O

• Entry DOI: 10.2210/pdb2y1o/pdb
• Related: 1E0D 1EEH 1UAG 2JFF 2JFG 2JFH 2UAG 2UUO 2UUP 2VTD 2VTE 2WJP 2X5O 3UAG 4UAG
• Descriptor: UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE, (2R)-2-[[3-[[4-[(Z)-(4-OXO-2-SULFANYLIDENE-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]PHENYL]METHYLAMINO]PHENYL]CARBONYLAMINO]PENTANEDIOIC ACID, DIMETHYL SULFOXIDE, ... (5 entities in total)
• Functional Keywords: ligase, cell cycle, cell division, cell shape, cell wall biogenesis/degradation
• Biological source: ESCHERICHIA COLI
• Cellular location: Cytoplasm: P14900
• Total number of polymer chains: 1
• Total formula weight: 49175.74

Authors

Tomasic, T.,Sink, R.,Kovac, A.,Turk, S.,Contreras-Martel, C.,Dessen, A.,Blanot, D.,Gobec, S.,Zega, A.,Kikelj, D.,Peterlin-Masic, L. (deposition date: 2010-12-09, release date: 2011-12-28, Last modification date: 2023-12-20)

Primary citation

Tomasic, T.,Sink, R.,Zidar, N.,Fic, A.,Contreras-Martel, C.,Dessen, A.,Patin, D.,Blanot, D.,Muller-Premru, M.,Gobec, S.,Zega, A.,Kikelj, D.,Masic, L.P.
Dual Inhibitor of MurD and MurE Ligases from Escherichia coli and Staphylococcus aureus.
ACS Med Chem Lett, 3:626-630, 2012

PubMed 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 μM) possessing antibacterial activity against Gram-positive S. aureus and its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) values of 8 μg/mL. The inhibitor was also found to be noncytotoxic for human HepG2 cells at concentrations below 200 μM.

PubMed: 24900523
DOI: 10.1021/ml300047h

Experimental method

X-RAY DIFFRACTION (1.49 Å)