5n0x
From Proteopedia
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==Crystal structure of OphA-DeltaC6 in complex with SAM== | ==Crystal structure of OphA-DeltaC6 in complex with SAM== | ||
| - | <StructureSection load='5n0x' size='340' side='right' caption='[[5n0x]], [[Resolution|resolution]] 1.67Å' scene=''> | + | <StructureSection load='5n0x' size='340' side='right'caption='[[5n0x]], [[Resolution|resolution]] 1.67Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5n0x]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N0X OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5n0x]] 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=5N0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N0X FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IML:N-METHYL-ISOLEUCINE'>IML</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5n0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n0x OCA], [https://pdbe.org/5n0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n0x RCSB], [https://www.ebi.ac.uk/pdbsum/5n0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n0x ProSAT]</span></td></tr> |
</table> | </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 peptide bond, the defining feature of proteins, governs peptide chemistry by abolishing nucleophilicity of the nitrogen. This and the planarity of the peptide bond arise from the delocalization of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl. While chemical methylation of an amide bond uses a strong base to generate the imidate, OphA, the precursor protein of the fungal peptide macrocycle omphalotin A, self-hypermethylates amides at pH 7 using S-adenosyl methionine (SAM) as cofactor. The structure of OphA reveals a complex catenane-like arrangement in which the peptide substrate is clamped with its amide nitrogen aligned for nucleophilic attack on the methyl group of SAM. Biochemical data and computational modeling suggest a base-catalyzed reaction with the protein stabilizing the reaction intermediate. Backbone N-methylation of peptides enhances their protease resistance and membrane permeability, a property that holds promise for applications to medicinal chemistry. | ||
| + | |||
| + | A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds.,Song H, van der Velden NS, Shiran SL, Bleiziffer P, Zach C, Sieber R, Imani AS, Krausbeck F, Aebi M, Freeman MF, Riniker S, Kunzler M, Naismith JH Sci Adv. 2018 Aug 24;4(8):eaat2720. doi: 10.1126/sciadv.aat2720. eCollection 2018, Aug. PMID:30151425<ref>PMID:30151425</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5n0x" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Omphalotus olearius]] |
| - | [[Category: | + | [[Category: Naismith JH]] |
| - | [[Category: | + | [[Category: Song H]] |
Current revision
Crystal structure of OphA-DeltaC6 in complex with SAM
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