PDBsum entry 6tsc

Transferase

PDB id: 6tsc

Contents

Protein chains

369 a.a.

12 a.a.

Ligands

SAH

Waters ×3

PDB id:

6tsc

Name:

Transferase

Title:

Ophma i407p complex with sah

Structure:

Peptide n-methyltransferase. Chain: a. Engineered: yes. Gly-phe-pro-trp-mva-ile-mva-val-gly-val-pro-gly. Chain: b. Engineered: yes

Source:

Omphalotus olearius. Organism_taxid: 72120. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Expression_system_taxid: 511693

Resolution:

2.19Å R-factor: 0.209 R-free: 0.232

Authors:

H.Song,J.H.Naismith

Key ref:

H.Song et al. (2020). Substrate Plasticity of a Fungal Peptide α-N-Methyltransferase. ACS Chem Biol, 15, 1901-1912. PubMed id: 32491837 DOI: 10.1021/acschembio.0c00237

Date:

20-Dec-19 Release date: 24-Jun-20

Protein chain

A0A2R2JFI5  (OPHMA_OMPOL) -  Methyltransferase/ribosomally synthesized cyclic peptide omphalotin A precursor ophMA from Omphalotus olearius

Seq: 417 a.a.

Struc: 369 a.a.

Protein chain

A0A2R2JFI5  (OPHMA_OMPOL) -  Methyltransferase/ribosomally synthesized cyclic peptide omphalotin A precursor ophMA from Omphalotus olearius

Seq: 417 a.a.

Struc: 12 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.1.1.- - ?????

DOI no: 10.1021/acschembio.0c00237

ACS Chem Biol 15:1901-1912 (2020)

PubMed id: 32491837

Substrate Plasticity of a Fungal Peptide α-N-Methyltransferase.

H.Song, J.R.Fahrig-Kamarauskaitè, E.Matabaro, H.Kaspar, S.L.Shirran, C.Zach, A.Pace, B.A.Stefanov, J.H.Naismith, M.Künzler.

ABSTRACT

The methylation of amide nitrogen atoms can improve the stability, oral availability, and cell permeability of peptide therapeutics. Chemical N-methylation of peptides is challenging. Omphalotin A is a ribosomally synthesized, macrocylic dodecapeptide with nine backbone N-methylations. The fungal natural product is derived from the precursor protein, OphMA, harboring both the core peptide and a SAM-dependent peptide α-N-methyltransferase domain. OphMA forms a homodimer and its α-N-methyltransferase domain installs the methyl groups in trans on the hydrophobic core dodecapeptide and some additional C-terminal residues of the protomers. These post-translational backbone N-methylations occur in a processive manner from the N- to the C-terminus of the peptide substrate. We demonstrate that OphMA can methylate polar, aromatic, and charged residues when these are introduced into the core peptide. Some of these amino acids alter the efficiency and pattern of methylation. Proline, depending on its sequence context, can act as a tunable stop signal. Crystal structures of OphMA variants have allowed rationalization of these observations. Our results hint at the potential to control this fungal α-N-methyltransferase for biotechnological applications.