8XU7
Crystal structure of Lsd18 in complex with a product
Summary for 8XU7
| Entry DOI | 10.2210/pdb8xu7/pdb |
| Descriptor | Putative epoxidase LasC, FLAVIN-ADENINE DINUCLEOTIDE, (4R,5S)-3-((2R,3S,4S)-2-ethyl-5-((2R,3R)-2-ethyl-3-(2-((2R,3R)-2-ethyl-3-methyloxiran-2-yl)ethyl)oxiran-2-yl)-3-hydroxy-4-methylpentanoyl)-4-methyl-5-phenyloxazolidin-2-one, ... (5 entities in total) |
| Functional Keywords | flavin-dependent monooxygenase, epoxidation, flavoprotein |
| Biological source | Streptomyces lasalocidi |
| Total number of polymer chains | 2 |
| Total formula weight | 108440.36 |
| Authors | Deng, Y.M.,Chen, X. (deposition date: 2024-01-12, release date: 2025-01-15, Last modification date: 2025-05-07) |
| Primary citation | Wang, Q.,Deng, Y.,Viera, D.,Liu, X.,Liu, N.,Hu, Y.,Hu, X.,Wei, H.,Zhou, Q.,Lan, T.,He, W.,Chen, X.,Kim, C.Y. Structural Basis of Sequential Enantioselective Epoxidation by a Flavin-Dependent Monooxygenase in Lasalocid A Biosynthesis. Angew.Chem.Int.Ed.Engl., :e202504982-e202504982, 2025 Cited by PubMed Abstract: Polyether polyketides are a structurally diverse group of natural products known for their antimicrobial and antiproliferative activities. Lasalocid A is a canonical natural polyether produced by the soil bacterium Streptomyces lasalocidi. In lasalocid A biosynthesis, a polyene polyketide intermediate is converted into a bisepoxide by the flavin-dependent monooxygenase enzyme Lsd18. Remarkably, Lsd18 acts on two distinct C═C groups in the substrate molecule, forming two (R,R) epoxides. We have determined the X-ray crystal structures of Lsd18 in the substrate-free, substrate-bound, and product-bound forms. Our work has revealed that Lsd18 has an extra-large substrate-binding pocket that allows the polyene to adopt different conformations within the enzyme pocket. This feature enables Lsd18 to epoxidate both of the C═C groups. Additionally, a subpocket located near the Lsd18 active site controls stereoselectivity by dictating which face of the C═C group is placed next to the flavin. Molecular understanding of how Lsd18 transforms a polyene into a bisepoxide during lasalocid A biosynthesis lays the foundation for the production of designer polyethers for drug development. PubMed: 40199722DOI: 10.1002/anie.202504982 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
Download full validation report
