7YWJ
Crystal structure of an engineered TycA variant, TycA pPLA (L313P)
Summary for 7YWJ
| Entry DOI | 10.2210/pdb7ywj/pdb |
| Descriptor | Tyrocidine synthase 1, SULFATE ION, 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total) |
| Functional Keywords | nonribosomal peptide synthetase, adenylation domain, depsipeptides, ligase |
| Biological source | Brevibacillus parabrevis |
| Total number of polymer chains | 2 |
| Total formula weight | 95739.53 |
| Authors | Mittl, P.,Camus, A.,Truong, G.,Markert, G.,Hilvert, D. (deposition date: 2022-02-14, release date: 2022-09-21, Last modification date: 2024-01-31) |
| Primary citation | Camus, A.,Truong, G.,Mittl, P.R.E.,Markert, G.,Hilvert, D. Reprogramming Nonribosomal Peptide Synthetases for Site-Specific Insertion of alpha-Hydroxy Acids. J.Am.Chem.Soc., 144:17567-17575, 2022 Cited by PubMed Abstract: High-throughput engineering has the potential to revolutionize the customization of biosynthetic assembly lines for the sustainable production of pharmaceutically relevant natural product analogs. Here, we show that the substrate specificity of gatekeeper adenylation domains of nonribosomal peptide synthetases can be switched from an α-amino acid to an α-hydroxy acid in a single round of combinatorial mutagenesis and selection using yeast cell surface display. In addition to shedding light on how such proteins discriminate between amino and hydroxy groups, the remodeled domains function in a pathway context to produce α-hydroxy acid-containing linear peptides and cyclic depsipeptides with high efficiency. Site-specific replacement of backbone amines with oxygens by an engineered synthetase provides the means to probe and tune the activities of diverse peptide metabolites in a simple and predictable fashion. PubMed: 36070491DOI: 10.1021/jacs.2c07013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.749 Å) |
Structure validation
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