1FVM

Complex of vancomycin with DI-acetyl-LYS-D-ALA-D-ALA

Summary for 1FVM

• Entry DOI: 10.2210/pdb1fvm/pdb
• Related: 1AA5 1C0Q 1C0R 1GAC 1GHG 1PN3 1PNV 1QD8 1RRV 1SHO
• Related PRD ID: PRD_000204
• Descriptor: VANCOMYCIN, DI-ACETYL-LYS-D-ALA-D-ALA, vancosamine-(1-2)-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: peptide-antibiotic complex, glycopeptide, antibiotic, vancomycin, cell wall precursor, structural protein-antibiotic complex, peptide/antibiotic
• Biological source: AMYCOLATOPSIS ORIENTALIS
• Total number of polymer chains: 12
• Total formula weight: 11074.40

Authors

Nitanai, Y.,Kakoi, K.,Aoki, K. (deposition date: 2000-09-20, release date: 2000-11-01, Last modification date: 2023-11-15)

Primary citation

Nitanai, Y.,Kikuchi, T.,Kakoi, K.,Hanamaki, S.,Fujisawa, I.,Aoki, K.
Crystal Structures of the Complexes between Vancomycin and Cell-Wall Precursor Analogs.
J.Mol.Biol., 385:1422-, 2009

PubMed Abstract: The crystal structures of three vancomycin complexes with two vancomycin-sensitive cell-wall precursor analogs (diacetyl-Lys-D-Ala-D-Ala and acetyl-D-Ala-D-Ala) and a vancomycin-resistant cell-wall precursor analog (diacetyl-Lys-D-Ala-D-lactate) were determined at atomic resolutions of 1.80 A, 1.07 A, and 0.93 A, respectively. These structures not only reconfirm the "back-to-back" dimerization of vancomycin monomers and the ligand-binding scheme proposed by previous experiments but also show important structural features of strategies for the generation of new glycopeptide antibiotics. These structural features involve a water-mediated antibiotic-ligand interaction and supramolecular structures such as "side-by-side" arranged dimer-to-dimer structures, in addition to ligand-mediated and "face-to-face" arranged dimer-to-dimer structures. In the diacetyl-Lys-D-Ala-D-lactate complex, the interatomic O...O distance between the carbonyl oxygen of the fourth residue of the antibiotic backbone and the ester oxygen of the D-lactate moiety of the ligand is clearly longer than the corresponding N-H...O hydrogen-bonding distance observed in the two other complexes due to electrostatic repulsion. In addition, two neighboring hydrogen bonds are concomitantly lengthened. These observations provide, at least in part, a molecular basis for the reduced antibacterial activity of vancomycin toward vancomycin-resistant bacteria with cell-wall precursors terminating in -D-Ala-D-lactate.

PubMed: 18976660
DOI: 10.1016/J.JMB.2008.10.026

Experimental method

X-RAY DIFFRACTION (1.8 Å)