8YSB
Crystal structure of DynA1, a putative monoxygenase from Mivromonospora chersina.
Summary for 8YSB
| Entry DOI | 10.2210/pdb8ysb/pdb |
| Descriptor | Predicted ester cyclase (1 entity in total) |
| Functional Keywords | anthraquinone-fused enediyne, two-enzyme system, anthraquinone formation, oxidoreductase, isomerase |
| Biological source | Micromonospora chersina |
| Total number of polymer chains | 1 |
| Total formula weight | 15708.98 |
| Authors | Yan, X.F.,Huang, H.W.,Gao, Y.G.,Liang, Z.X. (deposition date: 2024-03-22, release date: 2024-09-04, Last modification date: 2024-09-11) |
| Primary citation | Ma, G.L.,Liu, W.Q.,Huang, H.,Yan, X.F.,Shen, W.,Visitsatthawong, S.,Prakinee, K.,Tran, H.,Fan, X.,Gao, Y.G.,Chaiyen, P.,Li, J.,Liang, Z.X. An Enzymatic Oxidation Cascade Converts delta-Thiolactone Anthracene to Anthraquinone in the Biosynthesis of Anthraquinone-Fused Enediynes. Jacs Au, 4:2925-2935, 2024 Cited by PubMed Abstract: Anthraquinone-fused enediynes are anticancer natural products featuring a DNA-intercalating anthraquinone moiety. Despite recent insights into anthraquinone-fused enediyne (AQE) biosynthesis, the enzymatic steps involved in anthraquinone biogenesis remain to be elucidated. Through a combination of and studies, we demonstrated that a two-enzyme system, composed of a flavin adenine dinucleotide (FAD)-dependent monooxygenase (DynE13) and a cofactor-free enzyme (DynA1), catalyzes the final steps of anthraquinone formation by converting δ-thiolactone anthracene to hydroxyanthraquinone. We showed that the three oxygen atoms in the hydroxyanthraquinone originate from molecular oxygen (O), with the sulfur atom eliminated as HS. We further identified the key catalytic residues of DynE13 and A1 by structural and site-directed mutagenesis studies. Our data support a catalytic mechanism wherein DynE13 installs two oxygen atoms with concurrent desulfurization and decarboxylation, whereas DynA1 acts as a cofactor-free monooxygenase, installing the final oxygen atom in the hydroxyanthraquinone. These findings establish the indispensable roles of DynE13 and DynA1 in AQE biosynthesis and unveil novel enzymatic strategies for anthraquinone formation. PubMed: 39211597DOI: 10.1021/jacsau.4c00279 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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