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5n4d
From Proteopedia
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==Prolyl oligopeptidase B from Galerina marginata bound to 25mer macrocyclization substrate - D661A mutant== | ==Prolyl oligopeptidase B from Galerina marginata bound to 25mer macrocyclization substrate - D661A mutant== | ||
| - | <StructureSection load='5n4d' size='340' side='right' caption='[[5n4d]], [[Resolution|resolution]] 1.62Å' scene=''> | + | <StructureSection load='5n4d' size='340' side='right'caption='[[5n4d]], [[Resolution|resolution]] 1.62Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5n4d]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N4D OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5n4d]] 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=5N4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N4D 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]] 1.62Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <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'>[https://proteopedia.org/fgij/fg.htm?mol=5n4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4d OCA], [https://pdbe.org/5n4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n4d RCSB], [https://www.ebi.ac.uk/pdbsum/5n4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4d 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;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:29051530</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5n4d" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Galerina marginata]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Czekster CM]] |
| - | [[Category: | + | [[Category: Ludewig H]] |
| - | [[Category: | + | [[Category: McMahon SA]] |
| - | [[Category: | + | [[Category: Naismith JH]] |
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Current revision
Prolyl oligopeptidase B from Galerina marginata bound to 25mer macrocyclization substrate - D661A mutant
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