7lif

Aspartimidylated omega ester peptide fuscimiditide

spinqualitylabelsall models 7lif Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lif is a 1 chain structure with sequence from Thermobifida fusca YX. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q47NX9_THEFY Publication Abstract from PubMed Microviridins and other omega-ester-linked peptides, collectively known as graspetides, are characterized by side-chain-side-chain linkages installed by ATP-grasp enzymes. Here we report the discovery of a family of graspetides, the gene clusters of which also encode an O-methyltransferase with homology to the protein repair catalyst protein L-isoaspartyl methyltransferase. Using heterologous expression, we produced fuscimiditide, a ribosomally synthesized and post-translationally modified peptide (RiPP). NMR analysis of fuscimiditide revealed that the peptide contains two ester cross-links forming a stem-loop macrocycle. Furthermore, an unusually stable aspartimide moiety is found within the loop macrocycle. We fully reconstituted fuscimiditide biosynthesis in vitro including formation of the ester and aspartimide moieties. The aspartimide moiety embedded in fuscimiditide hydrolyses regioselectively to isoaspartate. Surprisingly, this isoaspartate-containing peptide is also a substrate for the L-isoaspartyl methyltransferase homologue, thus driving any hydrolysis products back to the aspartimide form. Whereas an aspartimide is often considered a nuisance product in protein formulations, our data suggest that some RiPPs have aspartimide residues intentionally installed via enzymatic activity. Biosynthesis and characterization of fuscimiditide, an aspartimidylated graspetide.,Elashal HE, Koos JD, Cheung-Lee WL, Choi B, Cao L, Richardson MA, White HL, Link AJ Nat Chem. 2022 Aug 18. pii: 10.1038/s41557-022-01022-y. doi:, 10.1038/s41557-022-01022-y. PMID:35982233 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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