6c0y | pdb_00006c0y

Lysinoalanine synthase, DurN, from duramycin biosynthesis bound to duramycin

spinqualitylabelsall models 6c0y, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6c0y is a 16 chain structure with sequence from "streptomyces_cinnamomeus_forma_cinnamomeus"_(sic)_pridham_et_al._1956 "streptomyces cinnamomeus forma cinnamomeus" (sic) pridham et al. 1956 and Streptomyces cinnamoneus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: K NonStd Res: BH2, DAL, DBB Gene: durN ("Streptomyces cinnamomeus forma cinnamomeus" (sic) Pridham et al. 1956) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Duramycin is a heavily post-translationally modified peptide that binds phosphatidylethanolamine. It has been investigated as an antibiotic, an inhibitor of viral entry, a therapeutic for cystic fibrosis, and a tumor and vasculature imaging agent. Duramycin contains a beta-hydroxylated Asp (Hya) and four macrocycles, including an essential lysinoalanine (Lal) cross-link. The mechanism of Lal formation is not known. Here we show that Lal is installed stereospecifically by DurN via addition of Lys19 to a dehydroalanine. The structure of DurN reveals an unusual dimer with a new fold. Surprisingly, in the structure of duramycin bound to DurN, no residues of the enzyme are near the Lal cross-link. Instead, Hya15 of the substrate makes interactions with Lal, suggesting it acts as a base to deprotonate Lys19 during catalysis. Biochemical data suggest that DurN preorganizes the reactive conformation of the substrate, such that the Hya15 of the substrate can serve as the catalytic base for Lal formation. Substrate-assisted enzymatic formation of lysinoalanine in duramycin.,An L, Cogan DP, Navo CD, Jimenez-Oses G, Nair SK, van der Donk WA Nat Chem Biol. 2018 Oct;14(10):928-933. doi: 10.1038/s41589-018-0122-4. Epub 2018, Sep 3. PMID:30177849 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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