8KDL
Crystal structure of LmbF in complex with PLP
Summary for 8KDL
| Entry DOI | 10.2210/pdb8kdl/pdb |
| Descriptor | Aminotransferase class I/II-fold pyridoxal phosphate-dependent enzyme, GLYCEROL (3 entities in total) |
| Functional Keywords | lincomycin, plp, biosynthesis, lyase |
| Biological source | Streptomyces lincolnensis |
| Total number of polymer chains | 2 |
| Total formula weight | 96930.82 |
| Authors | Mori, T.,Lyu, S.,Kadlcik, S.,Abe, I. (deposition date: 2023-08-09, release date: 2024-08-14, Last modification date: 2025-02-26) |
| Primary citation | Mori, T.,Moriwaki, Y.,Sakurada, K.,Lyu, S.,Kadlcik, S.,Janata, J.,Mazumdar, A.,Koberska, M.,Terada, T.,Kamenik, Z.,Abe, I. Molecular basis for the diversification of lincosamide biosynthesis by pyridoxal phosphate-dependent enzymes. Nat.Chem., 17:256-264, 2025 Cited by PubMed Abstract: The biosynthesis of the lincosamide antibiotics lincomycin A and celesticetin involves the pyridoxal-5'-phosphate (PLP)-dependent enzymes LmbF and CcbF, which are responsible for bifurcation of the biosynthetic pathways. Despite recognizing the same S-glycosyl-L-cysteine structure of the substrates, LmbF catalyses thiol formation through β-elimination, whereas CcbF produces S-acetaldehyde through decarboxylation-coupled oxidative deamination. The structural basis for the diversification mechanism remains largely unexplored. Here we conduct structure-function analyses of LmbF and CcbF. X-ray crystal structures, docking and molecular dynamics simulations reveal that active-site aromatic residues play important roles in controlling the substrate binding mode and the reaction outcome. Furthermore, the reaction selectivity and oxygen-utilization of LmbF and CcbF were rationally engineered through structure- and calculation-based mutagenesis. Thus, the catalytic function of CcbF was switched to that of LmbF, and, remarkably, both LmbF and CcbF variants gained the oxidative-amidation activity to produce an unnatural S-acetamide derivative of lincosamide. PubMed: 39643667DOI: 10.1038/s41557-024-01687-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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