Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB

Inseok Song, Younghyeon Kim, Jaeseung Yu, Su Yong Go, Hong Geun Lee, Woon Ju Song, Seokhee Kim

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Graspetides, also known as ω-ester-containing peptides (OEPs), are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) bearing side chain-to-side chain macrolactone or macrolactam linkages. Here, we present the molecular details of precursor peptide recognition by the macrocyclase enzyme PsnB in the biosynthesis of plesiocin, a group 2 graspetide. Biochemical analysis revealed that, in contrast to other RiPPs, the core region of the plesiocin precursor peptide noticeably enhanced the enzyme–precursor interaction via the conserved glutamate residues. We obtained four crystal structures of symmetric or asymmetric PsnB dimers, including those with a bound core peptide and a nucleotide, and suggest that the highly conserved Arg213 at the enzyme active site specifically recognizes a ring-forming acidic residue before phosphorylation. Collectively, this study provides insights into the mechanism underlying substrate recognition in graspetide biosynthesis and lays a foundation for engineering new variants. [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)1123-1131
Number of pages9
JournalNature Chemical Biology
Issue number11
StatePublished - Nov 2021


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