5n0x

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of OphA-DeltaC6 in complex with SAM

Structural highlights

5n0x is a 2 chain structure with sequence from Omphalotus olearius. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.67Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2] ^[3] ^[4]

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^[5]

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

References

↑ Ramm S, Krawczyk B, Mühlenweg A, Poch A, Mösker E, Süssmuth RD. A Self-Sacrificing N-Methyltransferase Is the Precursor of the Fungal Natural Product Omphalotin. Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9994-9997. PMID:28715095 doi:10.1002/anie.201703488
↑ 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. A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds. Sci Adv. 2018 Aug 24;4(8):eaat2720. doi: 10.1126/sciadv.aat2720. eCollection 2018, Aug. PMID:30151425 doi:http://dx.doi.org/10.1126/sciadv.aat2720
↑ Song H, Fahrig-Kamarauskaite JR, Matabaro E, Kaspar H, Shirran SL, Zach C, Pace A, Stefanov BA, Naismith JH, Kunzler M. Substrate Plasticity of a Fungal Peptide alpha-N-Methyltransferase. ACS Chem Biol. 2020 Jun 19. doi: 10.1021/acschembio.0c00237. PMID:32491837 doi:http://dx.doi.org/10.1021/acschembio.0c00237
↑ Matabaro E, Kaspar H, Dahlin P, Bader DLV, Murar CE, Staubli F, Field CM, Bode JW, Künzler M. Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A. Sci Rep. 2021 Feb 11;11(1):3541. PMID:33574430 doi:10.1038/s41598-021-83106-2
↑ 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. A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds. Sci Adv. 2018 Aug 24;4(8):eaat2720. doi: 10.1126/sciadv.aat2720. eCollection 2018, Aug. PMID:30151425 doi:http://dx.doi.org/10.1126/sciadv.aat2720

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n0x"

Categories: Large Structures | Omphalotus olearius | Naismith JH | Song H

@@ Line 3: / Line 3: @@
 <StructureSection load='5n0x' size='340' side='right'caption='[[5n0x]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n0x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Jack_o'lantern Jack o'lantern]. 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 [http://proteopedia.org/fgij/fg.htm?mol=5N0X FirstGlance]. <br>
+<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='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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=IML:N-METHYL-ISOLEUCINE'>IML</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr>
+<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'>[http://proteopedia.org/fgij/fg.htm?mol=5n0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n0x OCA], [http://pdbe.org/5n0x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n0x RCSB], [http://www.ebi.ac.uk/pdbsum/5n0x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n0x ProSAT]</span></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=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>
+== 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 ==
@@ Line 21: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Jack o'lantern]]
 [[Category: Large Structures]]
-[[Category: Naismith, J H]]
+[[Category: Omphalotus olearius]]
-[[Category: Song, H]]
+[[Category: Naismith JH]]
-[[Category: Methyltransferase]]
+[[Category: Song H]]
-[[Category: Transferase]]

5n0x

From Proteopedia

Current revision

Crystal structure of OphA-DeltaC6 in complex with SAM

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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