6E6T
Dieckmann cyclase, NcmC, bound to cerulenin
Summary for 6E6T
| Entry DOI | 10.2210/pdb6e6t/pdb |
| Descriptor | NcmC, SULFATE ION, (4S,5R)-4,5-dihydroxy-5-[(3E,6E)-octa-3,6-dien-1-yl]pyrrolidin-2-one, ... (4 entities in total) |
| Functional Keywords | dieckmann cyclase, off-loading, dieckmann condensation, lyase-antibiotic complex, lyase/antibiotic |
| Biological source | Saccharothrix syringae |
| Total number of polymer chains | 2 |
| Total formula weight | 58271.46 |
| Authors | Cogan, D.P.,Nair, S.K. (deposition date: 2018-07-25, release date: 2019-07-31, Last modification date: 2024-10-23) |
| 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 (1.6 Å) |
Structure validation
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