6PQF

Solution structure of OlvA(BCS)

Summary for 6PQF

• Entry DOI: 10.2210/pdb6pqf/pdb
• NMR Information: BMRB: 30630
• Descriptor: OlvA(BCS) (1 entity in total)
• Functional Keywords: lanthipeptide, ripps, ribosomal protein
• Biological source: Streptomyces olivaceus
• Total number of polymer chains: 1
• Total formula weight: 1616.84

Authors

Acedo, J.Z.,van der Donk, W.A. (deposition date: 2019-07-09, release date: 2019-10-23, Last modification date: 2024-11-06)

Primary citation

Acedo, J.Z.,Bothwell, I.R.,An, L.,Trouth, A.,Frazier, C.,van der Donk, W.A.
O-Methyltransferase-Mediated Incorporation of a beta-Amino Acid in Lanthipeptides.
J.Am.Chem.Soc., 141:16790-16801, 2019

PubMed Abstract: Lanthipeptides represent a large class of cyclic natural products defined by the presence of lanthionine (Lan) and methyllanthionine (MeLan) cross-links. With the advances in DNA sequencing technologies and genome mining tools, new biosynthetic enzymes capable of installing unusual structural features are continuously being discovered. In this study, we investigated an -methyltransferase that is a member of the most prominent auxiliary enzyme family associated with class I lanthipeptide biosynthetic gene clusters. Despite the prevalence of these enzymes, their function has not been established. Herein, we demonstrate that the -methyltransferase OlvS encoded in the gene cluster from NRRL B-3009 catalyzes the rearrangement of a highly conserved aspartate residue to a β-amino acid, isoaspartate, in the lanthipeptide OlvA(BCS). We elucidated the NMR solution structure of the GluC-digested peptide, OlvA(BCS), which revealed a unique ring topology comprising four interlocking rings and positions the isoaspartate residue in a solvent exposed loop that is stabilized by a MeLan ring. Gas chromatography-mass spectrometry analysis further indicated that OlvA(BCS) contains two dl-MeLan rings and two Lan rings with an unusual ll-stereochemistry. Lastly, in vitro reconstitution of OlvS activity showed that it is a leader peptide-independent and -adenosyl methionine-dependent -methyltransferase that mediates the conversion of a highly conserved aspartate residue in a cyclic substrate into a succinimide, which is hydrolyzed to generate an Asp or isoAsp containing peptide. This overall transformation converts an α-amino acid into a β-amino acid in a ribosomally synthesized peptide, via an electrophilic intermediate that may be the intended product.

PubMed: 31568727
DOI: 10.1021/jacs.9b07396

Experimental method

SOLUTION NMR