6pqf

From Proteopedia

Jump to: navigation, search

Solution structure of OlvA(BCS)

Structural highlights

6pqf is a 1 chain structure with sequence from Streptomyces olivaceus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR, 20 models
Ligands:DBB, IAS
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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 O-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 O-methyltransferase OlvSA encoded in the olv gene cluster from Streptomyces olivaceus NRRL B-3009 catalyzes the rearrangement of a highly conserved aspartate residue to a beta-amino acid, isoaspartate, in the lanthipeptide OlvA(BCSA). We elucidated the NMR solution structure of the GluC-digested peptide, OlvA(BCSA)(GluC), 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(BCSA) contains two dl-MeLan rings and two Lan rings with an unusual ll-stereochemistry. Lastly, in vitro reconstitution of OlvSA activity showed that it is a leader peptide-independent and S-adenosyl methionine-dependent O-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 alpha-amino acid into a beta-amino acid in a ribosomally synthesized peptide, via an electrophilic intermediate that may be the intended product.

O-Methyltransferase-Mediated Incorporation of a beta-Amino Acid in Lanthipeptides.,Acedo JZ, Bothwell IR, An L, Trouth A, Frazier C, van der Donk WA J Am Chem Soc. 2019 Oct 15. doi: 10.1021/jacs.9b07396. PMID:31568727[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Loading citation details..
Citations
reviews cite this structure
No citations found

References

  1. Acedo JZ, Bothwell IR, An L, Trouth A, Frazier C, van der Donk WA. O-Methyltransferase-Mediated Incorporation of a beta-Amino Acid in Lanthipeptides. J Am Chem Soc. 2019 Oct 15. doi: 10.1021/jacs.9b07396. PMID:31568727 doi:http://dx.doi.org/10.1021/jacs.9b07396

Contents


PDB ID 6pqf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools