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PDBsum entry 3dff
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References listed in PDB file
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Key reference
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Title
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Crystal structures of lipoglycopeptide antibiotic deacetylases: implications for the biosynthesis of a40926 and teicoplanin.
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Authors
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Y.Zou,
J.S.Brunzelle,
S.K.Nair.
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Ref.
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Chem Biol, 2008,
15,
533-545.
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PubMed id
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Abstract
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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.
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