2JFG

Crystal structure of MurD ligase in complex with UMA and ADP

Summary for 2JFG

• Entry DOI: 10.2210/pdb2jfg/pdb
• Related: 1E0D 1EEH 1UAG 2JFF 2JFH 2UAG 3UAG 4UAG
• Descriptor: UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE, URIDINE-5'-DIPHOSPHATE-N-ACETYLMURAMOYL-L-ALANINE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: nucleotide-binding, peptidoglycan synthesis, murd ligase, atp-binding, cell division, uma, adp, ligase, cell wall, cell shape, cell cycle
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 49253.16

Authors

Kotnik, M.,Humljan, J.,Contreras-Martel, C.,Oblak, M.,Kristan, K.,Herve, M.,Blanot, D.,Urleb, U.,Gobec, S.,Dessen, A.,Solmajer, T. (deposition date: 2007-02-01, release date: 2007-05-15, Last modification date: 2023-12-13)

Primary citation

Kotnik, M.,Humljan, J.,Contreras-Martel, C.,Oblak, M.,Kristan, K.,Herve, M.,Blanot, D.,Urleb, U.,Gobec, S.,Dessen, A.,Solmajer, T.
Structural and functional characterization of enantiomeric glutamic acid derivatives as potential transition state analogue inhibitors of MurD ligase.
J. Mol. Biol., 370:107-115, 2007

PubMed Abstract: Mur ligases play an essential role in the intracellular biosynthesis of bacterial peptidoglycan, the main component of the bacterial cell wall, and represent attractive targets for the design of novel antibacterials. UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) catalyses the addition of D-glutamic acid to the cytoplasmic intermediate UDP-N-acetylmuramoyl-L-alanine (UMA) and is the second in the series of Mur ligases. MurD ligase is highly stereospecific for its substrate, D-glutamic acid (D-Glu). Here, we report the high resolution crystal structures of MurD in complexes with two novel inhibitors designed to mimic the transition state of the reaction, which contain either the D-Glu or the L-Glu moiety. The binding modes of N-sulfonyl-D-Glu and N-sulfonyl-L-Glu derivatives were also characterised kinetically. The results of this study represent an excellent starting point for further development of novel inhibitors of this enzyme.

PubMed: 17507028
DOI: 10.1016/j.jmb.2007.04.048

Experimental method

X-RAY DIFFRACTION (1.52 Å)