6AZT
Asparaginyl endopeptidase 1 bound to AAN peptide, a tetrahedral intermediate
Summary for 6AZT
| Entry DOI | 10.2210/pdb6azt/pdb |
| Descriptor | Asparaginyl endopeptidase 1, ALA-ALA-ASN tetrahedral intermediate, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | plant protein |
| Biological source | Helianthus annuus (Common sunflower) More |
| Total number of polymer chains | 2 |
| Total formula weight | 54888.90 |
| Authors | Bond, C.S. (deposition date: 2017-09-13, release date: 2018-02-07, Last modification date: 2023-11-15) |
| Primary citation | Haywood, J.,Schmidberger, J.W.,James, A.M.,Nonis, S.G.,Sukhoverkov, K.V.,Elias, M.,Bond, C.S.,Mylne, J.S. Structural basis of ribosomal peptide macrocyclization in plants. Elife, 7:-, 2018 Cited by PubMed Abstract: Constrained, cyclic peptides encoded by plant genes represent a new generation of drug leads. Evolution has repeatedly recruited the Cys-protease asparaginyl endopeptidase (AEP) to perform their head-to-tail ligation. These macrocyclization reactions use the substrates amino terminus instead of water to deacylate, so a peptide bond is formed. How solvent-exposed plant AEPs macrocyclize is poorly understood. Here we present the crystal structure of an active plant AEP from the common sunflower, . The active site contained electron density for a tetrahedral intermediate with partial occupancy that predicted a binding mode for peptide macrocyclization. By substituting catalytic residues we could alter the ratio of cyclic to acyclic products. Moreover, we showed AEPs from other species lacking cyclic peptides can perform macrocyclization under favorable pH conditions. This structural characterization of AEP presents a logical framework for engineering superior enzymes that generate macrocyclic peptide drug leads. PubMed: 29384475DOI: 10.7554/eLife.32955 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
Download full validation report
