1HHU

Balhimycin in complex with D-Ala-D-Ala

Summary for 1HHU

• Entry DOI: 10.2210/pdb1hhu/pdb
• Related: 1GO6 1HHY 1HHZ
• Related PRD ID: PRD_000484
• Descriptor: BALHIMYCIN, beta-D-glucopyranose, (2R,4S,6S)-4-azanyl-4,6-dimethyl-oxane-2,5,5-triol, ... (7 entities in total)
• Functional Keywords: antibiotic, glycopeptide, cell wall peptides
• Biological source: AMYCOLATOPSIS SP.
• Total number of polymer chains: 4
• Total formula weight: 7939.04

Authors

Lehmann, C.,Bunkoczi, G.,Sheldrick, G.M.,Vertessy, L. (deposition date: 2000-12-28, release date: 2003-09-05, Last modification date: 2023-11-15)

Primary citation

Lehmann, C.,Bunkoczi, G.,Vertesy, L.,Sheldrick, G.M.
Structures of Glycopeptide Antibiotics with Peptides that Model Bacterial Cell-Wall Precursors
J.Mol.Biol., 318:723-, 2002

PubMed Abstract: The vancomycin-related antibiotics balhimycin and degluco-balhimycin have been crystallized in complexes with di-, tri- and pentapeptides that emulate bacterial cell-wall precursors, and four structures determined at atomic resolution (<1 A). In addition to the features expected from previous structural and spectroscopic studies, two new motifs were observed that may prove important in the design of antibiotics modified to overcome bacterial resistance. A changed binding mode was found in two dipeptide complexes, and a new type of face-to-face oligomerization (in addition to the well-established back-to-back dimerization) was seen when the model peptide reaches a critical fraction of the size of the cell-wall precursor pentapeptide. The extensive interactions involving both antibiotic and peptide molecules in this interface should appreciably enhance the kinetic and thermodynamic stability of the complexes. In the pentapeptide complex, the relative positions of the peptides are close to those required for d-Ala elimination, so this structure may provide a realistic model for the prevention of the enzyme-catalyzed cell-wall crosslinking by antibiotic binding.

PubMed: 12054818
DOI: 10.1016/S0022-2836(02)00146-8

Experimental method

X-RAY DIFFRACTION (0.89 Å)