2og6
From Proteopedia
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Crystal structure of asparagine oxygenase in complex with Fe(II)
Overview
Non-ribosomally synthesized lipopeptide antibiotics of the daptomycin type, are known to contain unnatural beta-modified amino acids, which are, essential for bioactivity. Here we present the biochemical and structural, basis for the incorporation of 3-hydroxyasparagine at position 9 in the, 11-residue acidic lipopeptide lactone calcium-dependent antibiotic (CDA)., Direct hydroxylation of l-asparagine by AsnO, a non-heme, Fe(2+)/alpha-ketoglutarate-dependent oxygenase encoded by the CDA, biosynthesis gene cluster, was validated by Fmoc derivatization of the, reaction product and LC/MS analysis. The 1.45, 1.92, and 1.66 A crystal, structures of AsnO as apoprotein, Fe(2+) complex, and product complex, respectively, with (2S,3S)-3-hydroxyasparagine and succinate revealed the, stereoselectivity and substrate specificity of AsnO. The comparison of, native and product-complex structures of AsnO showed a lid-like region, (residues F208-E223) that seals the active site upon substrate binding and, shields it from sterically demanding peptide substrates. Accordingly, beta-hydroxylated asparagine is synthesized prior to its incorporation, into the growing CDA peptide. The AsnO structure could serve as a template, for engineering novel enzymes for the synthesis of beta-hydroxylated amino, acids.
About this Structure
2OG6 is a Single protein structure of sequence from Bacteria with and as ligands. Full crystallographic information is available from OCA.
Reference
Mechanistic and structural basis of stereospecific Cbeta-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide., Strieker M, Kopp F, Mahlert C, Essen LO, Marahiel MA, ACS Chem Biol. 2007 Mar 20;2(3):187-96. PMID:17373765
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