6E6U
Variant C89S of Dieckmann cyclase, NcmC
Summary for 6E6U
| Entry DOI | 10.2210/pdb6e6u/pdb |
| Descriptor | Dieckmann cyclase, NcmC, SULFATE ION (3 entities in total) |
| Functional Keywords | dieckmann cyclase, off-loading, dieckmann condensation, biosynthetic protein |
| Biological source | Saccharothrix syringae |
| Total number of polymer chains | 2 |
| Total formula weight | 57788.76 |
| Authors | Cogan, D.P.,Nair, S.K. (deposition date: 2018-07-25, release date: 2019-07-31, Last modification date: 2023-10-11) |
| Primary citation | Cogan, D.P.,Ly, J.,Nair, S.K. Structural Basis for Enzymatic Off-Loading of Hybrid Polyketides by Dieckmann Condensation. Acs Chem.Biol., 2020 Cited by PubMed Abstract: While several bioactive natural products that contain tetramate or pyridone heterocycles have been described, information on the enzymology underpinning these functionalities has been limited. Here we biochemically characterize an off-loading Dieckmann cyclase, NcmC, that installs the tetramate headgroup in nocamycin, a hybrid polyketide/nonribosomal peptide natural product. Crystal structures of the enzyme (1.6 Å) and its covalent complex with the epoxide cerulenin (1.6 Å) guide additional structure-based mutagenesis and product-profile analyses. Our results offer mechanistic insights into how the conserved thioesterase-like scaffold has been adapted to perform a new chemical reaction, namely, heterocyclization. Additional bioinformatics combined with docking and modeling identifies likely candidates for heterocycle formation in underexplored gene clusters and uncovers a modular basis of substrate recognition by the two subdomains of these Dieckmann cyclases. PubMed: 33017142DOI: 10.1021/acschembio.0c00579 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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