2X5O

Discovery of Novel 5-Benzylidenerhodanine- and 5-Benzylidene- thiazolidine-2,4-dione Inhibitors of MurD Ligase

Summary for 2X5O

• Entry DOI: 10.2210/pdb2x5o/pdb
• Related: 1E0D 1EEH 1UAG 2JFF 2JFG 2JFH 2UAG 2UUO 2UUP 2VTD 2VTE 2WJP 3UAG 4UAG
• Descriptor: UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE, N-({3-[({4-[(Z)-(2,4-DIOXO-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]PHENYL}AMINO)METHYL]PHENYL}CARBONYL)-D-GLUTAMIC ACID, AZIDE ION, ... (7 entities in total)
• Functional Keywords: atp-binding, cell cycle, cell division, cell shape, cell wall biogenesis/degradation, ligase, peptidoglycan synthesis
• Biological source: Escherichia coli DH5[alpha]
• Cellular location: Cytoplasm: P14900
• Total number of polymer chains: 1
• Total formula weight: 48096.99

Authors

Zidar, N.,Tomasic, T.,Sink, R.,Rupnik, V.,Kovac, A.,Turk, S.,Contreras-Martel, C.,Dessen, A.,Blanot, D.,Gobec, S.,Zega, A.,Peterlin-Masic, L.,Kikelja, D. (deposition date: 2010-02-10, release date: 2010-09-15, Last modification date: 2023-12-20)

Primary citation

Zidar, N.,Tomasic, T.,Sink, R.,Rupnik, V.,Kovac, A.,Turk, S.,Patin, D.,Blanot, D.,Contreras Martel, C.,Dessen, A.,Muller Premru, M.,Zega, A.,Gobec, S.,Peterlin Masic, L.,Kikelj, D.
Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase.
J. Med. Chem., 53:6584-6594, 2010

PubMed Abstract: We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC(50) in the range 45-206 μM. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.

PubMed: 20804196
DOI: 10.1021/jm100285g

Experimental method

X-RAY DIFFRACTION (1.46 Å)