Files in this item
Substrate plasticity of a fungal peptide α-N-methyltransferase
Item metadata
dc.contributor.author | Song, Haigang | |
dc.contributor.author | Fahrig-Kamarauskaite, Jurate | |
dc.contributor.author | Matabaro, Emmanuel | |
dc.contributor.author | Kaspar, Hannelore | |
dc.contributor.author | Shirran, Sally L. | |
dc.contributor.author | Zach, Christina | |
dc.contributor.author | Pace, Amy | |
dc.contributor.author | Stefanov, Bozhidar-Adrian | |
dc.contributor.author | Naismith, James H. | |
dc.contributor.author | Kunzler, Markus | |
dc.date.accessioned | 2020-08-06T14:30:03Z | |
dc.date.available | 2020-08-06T14:30:03Z | |
dc.date.issued | 2020-07-17 | |
dc.identifier | 269484747 | |
dc.identifier | b317f870-2223-4d56-9be8-09445a6c2ebc | |
dc.identifier | 000551550000023 | |
dc.identifier | 85087727746 | |
dc.identifier.citation | Song , H , Fahrig-Kamarauskaite , J , Matabaro , E , Kaspar , H , Shirran , S L , Zach , C , Pace , A , Stefanov , B-A , Naismith , J H & Kunzler , M 2020 , ' Substrate plasticity of a fungal peptide α-N-methyltransferase ' , ACS Chemical Biology , vol. 15 , no. 7 , pp. 1901-1912 . https://doi.org/10.1021/acschembio.0c00237 | en |
dc.identifier.issn | 1554-8929 | |
dc.identifier.other | ORCID: /0000-0003-3516-3507/work/78527686 | |
dc.identifier.uri | https://hdl.handle.net/10023/20417 | |
dc.description | This work was financially supported by the Commission for Technology and Innovation (CTI/Innosuisse Grant No. CTI 25951.2), the Swiss National Science Foundation (Grant No. 31003A_173097), Wellcome Trust (Grant No. 094476/Z/10/ Z), and BBSRC (Grant No. BB/R018189/1). | en |
dc.description.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. | |
dc.format.extent | 12 | |
dc.format.extent | 7590820 | |
dc.language.iso | eng | |
dc.relation.ispartof | ACS Chemical Biology | en |
dc.subject | QH301 Biology | en |
dc.subject | NDAS | en |
dc.subject.lcc | QH301 | en |
dc.title | Substrate plasticity of a fungal peptide α-N-methyltransferase | en |
dc.type | Journal article | en |
dc.contributor.sponsor | The Wellcome Trust | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.identifier.doi | 10.1021/acschembio.0c00237 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 094476/Z/10/Z | en |
This item appears in the following Collection(s)
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.