1E4E

D-alanyl-D-lacate ligase

Summary for 1E4E

• Entry DOI: 10.2210/pdb1e4e/pdb
• Related: 1IOV 1IOW
• Descriptor: VANCOMYCIN/TEICOPLANIN A-TYPE RESISTANCE PROTEIN VANA, ADENOSINE-5'-DIPHOSPHATE, 1(S)-AMINOETHYL-(2-CARBOXYPROPYL)PHOSPHORYL-PHOSPHINIC ACID, ... (8 entities in total)
• Functional Keywords: ligase, cell wall, antibiotic resistance, membrane, peptidoglycan synthesis
• Biological source: ENTEROCOCCUS FAECIUM; More
• Total number of polymer chains: 2
• Total formula weight: 78272.58

Authors

Roper, D.I. (deposition date: 2000-07-03, release date: 2001-06-28, Last modification date: 2024-10-09)

Primary citation

Roper, D.I.,Huyton, T.,Vagin, A.,Dodson, G.
The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA).
Proc. Natl. Acad. Sci. U.S.A., 97:8921-8925, 2000

PubMed Abstract: d-alanine-d-lactate ligase from Enterococcus faecium BM4147 is directly responsible for the biosynthesis of alternate cell-wall precursors in bacteria, which are resistant to the glycopeptide antibiotic vancomycin. The crystal structure has been determined with data extending to 2.5-A resolution. This structure shows that the active site has unexpected interactions and is distinct from previous models for d-alanyl-d-lactate ligase mechanistic studies. It appears that the preference of the enzyme for lactate as a ligand over d-alanine could be mediated by electrostatic effects and/or a hydrogen-bonding network, which principally involve His-244. The structure of d-alanyl-d-lactate ligase provides a revised interpretation of the molecular events that lead to vancomycin resistance.

PubMed: 10908650
DOI: 10.1073/pnas.150116497

Experimental method

X-RAY DIFFRACTION (2.5 Å)