View source for 6qzz


==full length OphA V404E in complex with SAH==
<StructureSection load='6qzz' size='340' side='right'caption='[[6qzz]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qzz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Omphalotus_olearius Omphalotus olearius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QZZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EME:N-METHYL-L-GLUTAMIC+ACID'>EME</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6qzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qzz OCA], [https://pdbe.org/6qzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qzz RCSB], [https://www.ebi.ac.uk/pdbsum/6qzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qzz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OPHMA_OMPOL OPHMA_OMPOL] Fusion protein of the methyltransferase ophM and the omphalotin core peptide; part of the gene cluster that mediates the biosynthesis of omphalotin A, a highly methylated cyclic dodecapeptide with nematodicidal activity (PubMed:28715095, PubMed:30151425, PubMed:32491837, PubMed:33574430). Omphalotin A derives from the C-terminus of the ophMA protein, and it is the ophMA protein that methylates its own C-terminus using S-adenosyl methionine (SAM) (PubMed:28715095, PubMed:30151425, PubMed:32491837, PubMed:33574430). The C-terminus is subsequently cleaved off and macrocyclized by the prolyloligopeptidase ophP to give the final product (PubMed:28715095, PubMed:30151425, PubMed:32491837).<ref>PMID:28715095</ref> <ref>PMID:30151425</ref> <ref>PMID:32491837</ref> <ref>PMID:33574430</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 alpha-N-methyltransferase domain. OphMA forms a homodimer and its alpha-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 alpha-N-methyltransferase for biotechnological applications.

Substrate Plasticity of a Fungal Peptide alpha-N-Methyltransferase.,Song H, Fahrig-Kamarauskaite JR, Matabaro E, Kaspar H, Shirran SL, Zach C, Pace A, Stefanov BA, Naismith JH, Kunzler M ACS Chem Biol. 2020 Jun 19. doi: 10.1021/acschembio.0c00237. PMID:32491837<ref>PMID:32491837</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qzz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Omphalotus olearius]]
[[Category: Naismith JH]]
[[Category: Song H]]