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| | <StructureSection load='5n4e' size='340' side='right'caption='[[5n4e]], [[Resolution|resolution]] 2.90Å' scene=''> | | <StructureSection load='5n4e' size='340' side='right'caption='[[5n4e]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5n4e]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Galerina_marginata Galerina marginata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N4E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5n4e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Galerina_marginata Galerina marginata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N4E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2.9Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POPB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=109633 Galerina marginata])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5n4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4e OCA], [http://pdbe.org/5n4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n4e RCSB], [http://www.ebi.ac.uk/pdbsum/5n4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4e 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=5n4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4e OCA], [https://pdbe.org/5n4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n4e RCSB], [https://www.ebi.ac.uk/pdbsum/5n4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/POPB_GALM3 POPB_GALM3] Dual function macrocyclase-peptidase involved in the biosynthesis of the highly toxic amanitin toxin family of macrocycles (PubMed:22202811, PubMed:28866879, PubMed:29051530). Cleaves peptide bonds on the C-terminal side of prolyl residues (PubMed:29051530). The enzyme first removes 10 residues from the N-terminus of a 35-residue substrate (PubMed:29051530). Conformational trapping of the 25 amino-acid peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization (PubMed:29051530). The enzyme rebinds the 25 amino-acid peptide in a different conformation and catalyzes macrocyclization of the N-terminal eight residues (PubMed:28866879, PubMed:29051530).<ref>PMID:22202811</ref> <ref>PMID:28866879</ref> <ref>PMID:29051530</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Galerina marginata]] | | [[Category: Galerina marginata]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Czekster, C M]] | + | [[Category: Czekster CM]] |
| - | [[Category: Ludewig, H]] | + | [[Category: Ludewig H]] |
| - | [[Category: McMahon, S A]] | + | [[Category: McMahon SA]] |
| - | [[Category: Naismith, J H]] | + | [[Category: Naismith JH]] |
| - | [[Category: Amanitin biosynthesis]]
| + | |
| - | [[Category: Beta-propeller]]
| + | |
| - | [[Category: Closed form]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Macrocyclase]]
| + | |
| - | [[Category: Peptidase]]
| + | |
| - | [[Category: Prolyl oligopeptidase]]
| + | |
| Structural highlights
Function
POPB_GALM3 Dual function macrocyclase-peptidase involved in the biosynthesis of the highly toxic amanitin toxin family of macrocycles (PubMed:22202811, PubMed:28866879, PubMed:29051530). Cleaves peptide bonds on the C-terminal side of prolyl residues (PubMed:29051530). The enzyme first removes 10 residues from the N-terminus of a 35-residue substrate (PubMed:29051530). Conformational trapping of the 25 amino-acid peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization (PubMed:29051530). The enzyme rebinds the 25 amino-acid peptide in a different conformation and catalyzes macrocyclization of the N-terminal eight residues (PubMed:28866879, PubMed:29051530).[1] [2] [3]
Publication Abstract from PubMed
Peptide macrocycles are promising therapeutic molecules because they are protease resistant, structurally rigid, membrane permeable, and capable of modulating protein-protein interactions. Here, we report the characterization of the dual function macrocyclase-peptidase enzyme involved in the biosynthesis of the highly toxic amanitin toxin family of macrocycles. The enzyme first removes 10 residues from the N-terminus of a 35-residue substrate. Conformational trapping of the 25 amino-acid peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization. The enzyme rebinds the 25 amino-acid peptide in a different conformation and catalyzes macrocyclization of the N-terminal eight residues. Structures of the enzyme bound to both substrates and biophysical analysis characterize the different binding modes rationalizing the mechanism. Using these insights simpler substrates with only five C-terminal residues were designed, allowing the enzyme to be more effectively exploited in biotechnology.
Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates.,Czekster CM, Ludewig H, McMahon SA, Naismith JH Nat Commun. 2017 Oct 19;8(1):1045. doi: 10.1038/s41467-017-00862-4. PMID:29051530[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Luo H, Hallen-Adams HE, Scott-Craig JS, Walton JD. Ribosomal biosynthesis of α-amanitin in Galerina marginata. Fungal Genet Biol. 2012 Feb;49(2):123-9. PMID:22202811 doi:10.1016/j.fgb.2011.12.005
- ↑ Sgambelluri RM, Smith MO, Walton JD. Versatility of Prolyl Oligopeptidase B in Peptide Macrocyclization. ACS Synth Biol. 2018 Jan 19;7(1):145-152. PMID:28866879 doi:10.1021/acssynbio.7b00264
- ↑ Czekster CM, Ludewig H, McMahon SA, Naismith JH. Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates. Nat Commun. 2017 Oct 19;8(1):1045. doi: 10.1038/s41467-017-00862-4. PMID:29051530 doi:http://dx.doi.org/10.1038/s41467-017-00862-4
- ↑ Czekster CM, Ludewig H, McMahon SA, Naismith JH. Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates. Nat Commun. 2017 Oct 19;8(1):1045. doi: 10.1038/s41467-017-00862-4. PMID:29051530 doi:http://dx.doi.org/10.1038/s41467-017-00862-4
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