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Crystal Structures of Lipoglycopeptide Antibiotic Deacetylases: Implications for the Biosynthesis of A40926 and Teicoplanin
- Source :
-
Chemistry & Biology . Jun2008, Vol. 15 Issue 6, p533-545. 13p. - Publication Year :
- 2008
-
Abstract
- Summary: The lipoglycopeptide antibiotics teicoplanin and A40926 have proven efficacy against Gram-positive pathogens. These drugs are distinguished from glycopeptide antibiotics by N-linked long chain acyl-D-glucosamine decorations that contribute to antibacterial efficacy. During the biosynthesis of lipoglycopeptides, tailoring glycosyltransferases attach an N-acetyl-D-glucosamine to the aglycone, and this N-acetyl-glucosaminyl pseudoaglycone is deacetylated prior to long chain hydrocarbon attachment. Here we present several high-resolution crystal structures of the pseudoaglycone deacetylases from the biosynthetic pathways of teicoplanin and A40926. The cocrystal structure of the teicoplanin pseudoaglycone deacetylase with a fatty acid product provides further insights into the roles of active-site residues, and suggests mechanistic similarities with structurally distinct zinc deacetylases, such as peptidoglycan deacetylase and LpxC. A unique, structurally mobile capping lid, located at the apex of these pseudoaglycone deacetylases, likely serves as a determinant of substrate specificity. [Copyright &y& Elsevier]
- Subjects :
- *ANTIBIOTICS
*ANTI-infective agents
*PATHOGENIC microorganisms
*GLUCOSAMINE
Subjects
Details
- Language :
- English
- ISSN :
- 10745521
- Volume :
- 15
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Chemistry & Biology
- Publication Type :
- Academic Journal
- Accession number :
- 32646040
- Full Text :
- https://doi.org/10.1016/j.chembiol.2008.05.009