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5n4c

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Prolyl oligopeptidase B from Galerina marginata bound to 35mer hydrolysis and macrocyclization substrate - S577A mutant

Structural highlights

5n4c is a 8 chain structure with sequence from Galerina marginata. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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/5n4c"

@@ Line 1: / Line 1: @@
 ==Prolyl oligopeptidase B from Galerina marginata bound to 35mer hydrolysis and macrocyclization substrate - S577A mutant==
-<StructureSection load='5n4c' size='340' side='right' caption='[[5n4c]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
+<StructureSection load='5n4c' size='340' side='right'caption='[[5n4c]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n4c]] is a 8 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=5N4C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N4C FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n4c]] is a 8 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=5N4C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N4C 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]] 2.19&#8491;</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=5n4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4c OCA], [http://pdbe.org/5n4c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n4c RCSB], [http://www.ebi.ac.uk/pdbsum/5n4c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4c 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=5n4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4c OCA], [https://pdbe.org/5n4c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n4c RCSB], [https://www.ebi.ac.uk/pdbsum/5n4c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4c ProSAT]</span></td></tr>
 </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 ==
@@ Line 22: / Line 24: @@
 </StructureSection>
 [[Category: Galerina marginata]]
-[[Category: Czekster, C M]]
+[[Category: Large Structures]]
-[[Category: Ludewig, H]]
+[[Category: Czekster CM]]
-[[Category: McMahon, S A]]
+[[Category: Ludewig H]]
-[[Category: Naismith, J H]]
+[[Category: McMahon SA]]
-[[Category: Amanitin biosynthesis]]
+[[Category: Naismith JH]]
-[[Category: Beta-propeller]]
-[[Category: Closed form]]
-[[Category: Hydrolase]]
-[[Category: Macrocyclase]]
-[[Category: Peptidase]]
-[[Category: Prolyl oligopeptidase]]

5n4c

From Proteopedia

Current revision

Prolyl oligopeptidase B from Galerina marginata bound to 35mer hydrolysis and macrocyclization substrate - S577A mutant

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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