7DRP

Structure of ATP-grasp ligase PsnB complexed with phosphomimetic variant of minimal precursor, Mg, and ADP

Summary for 7DRP

• Entry DOI: 10.2210/pdb7drp/pdb
• Descriptor: ATP-grasp domain-containing protein, PsnA214-38, Precursor peptide, phospho-mimic, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: atp-grasp ligase, ligase, ripp, graspetide, omega ester bond containing peptide
• Biological source: Plesiocystis pacifica SIR-1; More
• Total number of polymer chains: 6
• Total formula weight: 155362.26

Authors

Song, I.,Yu, J.,Song, W.,Kim, S. (deposition date: 2020-12-29, release date: 2021-09-08, Last modification date: 2023-11-29)

Primary citation

Song, I.,Kim, Y.,Yu, J.,Go, S.Y.,Lee, H.G.,Song, W.J.,Kim, S.
Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB.
Nat.Chem.Biol., 17:1123-1131, 2021

PubMed Abstract: 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.

PubMed: 34475564
DOI: 10.1038/s41589-021-00855-x

Experimental method

X-RAY DIFFRACTION (2.98 Å)