5A5F

CRYSTAL STRUCTURE OF MURD LIGASE FROM ESCHERICHIA COLI IN COMPLEX WITH UMA AND ADP

Summary for 5A5F

• Entry DOI: 10.2210/pdb5a5f/pdb
• Related: 5A5E
• Descriptor: UDP-N-ACETYLMURAMOYLALANINE--D-GLUTAMATE LIGASE, URIDINE-5'-DIPHOSPHATE-N-ACETYLMURAMOYL-L-ALANINE, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: ligase, peptidoglycan synthesis, adp-forming enzyme, cell wall, cell shape, cell cycle, nucleotide-binding, atp- binding, cell division, ligand, conformation
• Biological source: Escherichia coli K-12
• Cellular location: Cytoplasm: P14900
• Total number of polymer chains: 1
• Total formula weight: 48358.12

Authors

Sink, R.,Kotnik, M.,Zega, A.,Barreteau, H.,Gobec, S.,Blanot, D.,Dessen, A.,Contreras-Martel, C. (deposition date: 2015-06-17, release date: 2016-04-13, Last modification date: 2024-11-13)

Primary citation

Sink, R.,Kotnik, M.,Zega, A.,Barreteau, H.,Gobec, S.,Blanot, D.,Dessen, A.,Contreras-Martel, C.
Crystallographic Study of Peptidoglycan Biosynthesis Enzyme MurD: Domain Movement Revisited.
PLoS ONE, 11:e0152075-e0152075, 2016

PubMed Abstract: The biosynthetic pathway of peptidoglycan, an essential component of bacterial cell wall, is a well-recognized target for antibiotic development. Peptidoglycan precursors are synthesized in the bacterial cytosol by various enzymes including the ATP-hydrolyzing Mur ligases, which catalyze the stepwise addition of amino acids to a UDP-MurNAc precursor to yield UDP-MurNAc-pentapeptide. MurD catalyzes the addition of D-glutamic acid to UDP-MurNAc-L-Ala in the presence of ATP; structural and biochemical studies have suggested the binding of the substrates with an ordered kinetic mechanism in which ligand binding inevitably closes the active site. In this work, we challenge this assumption by reporting the crystal structures of intermediate forms of MurD either in the absence of ligands or in the presence of small molecules. A detailed analysis provides insight into the events that lead to the closure of MurD and reveals that minor structural modifications contribute to major overall conformation alterations. These novel insights will be instrumental in the development of new potential antibiotics designed to target the peptidoglycan biosynthetic pathway.

PubMed: 27031227
DOI: 10.1371/journal.pone.0152075

Experimental method

X-RAY DIFFRACTION (1.9 Å)