5N4B
Prolyl oligopeptidase B from Galerina marginata bound to 25mer macrocyclization substrate - S577A mutant
Summary for 5N4B
Entry DOI | 10.2210/pdb5n4b/pdb |
Descriptor | Prolyl oligopeptidase, Alpha-amanitin proprotein (3 entities in total) |
Functional Keywords | amanitin biosynthesis, prolyl oligopeptidase, macrocyclase, peptidase, beta-propeller, closed form, hydrolase |
Biological source | Galerina marginata More |
Total number of polymer chains | 4 |
Total formula weight | 169239.22 |
Authors | Czekster, C.M.,McMahon, S.A.,Ludewig, H.,Naismith, J.H. (deposition date: 2017-02-10, release date: 2017-11-01, Last modification date: 2024-01-17) |
Primary citation | Czekster, C.M.,Ludewig, H.,McMahon, S.A.,Naismith, J.H. Characterization of a dual function macrocyclase enables design and use of efficient macrocyclization substrates. Nat Commun, 8:1045-1045, 2017 Cited by PubMed Abstract: 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. PubMed: 29051530DOI: 10.1038/s41467-017-00862-4 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.44 Å) |
Structure validation
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