The anthracyclines are a class of highly effective natural product chemotherapeutics and are used to treat a range of cancers, including leukemia. Toxicity of the anthracyclines has stimulated efforts to further diversify the natural product’s scaffold, which has led to a renewed interest in the biosynthetic pathway responsible for formation and modification of this family of molecules. DnmZ, the focus of this study, is a flavin-dependent monooxygenase homologous to several newly characterized nitrososynthases. Its specific role in the anthracycline biosynthetic pathway is unknown, and may involve synthesis of the seven-carbon acetal moiety attached to C-4 of L-daunosamine observed in the anthracycline, baumycin. Herein, we utilize x-ray crystallography to elucidate the three dimensional structure of DnmZ. Our work yielded two crystal structures of DnmZ: the enzyme alone, solved to 3.0 Å resolution, and the enzyme in complex with thymidine diphosphate, the nucleotide carrier portion of the expected substrate, solved to 2.75 Å resolution. Comparison of these structures allowed identification of conformational changes that may occur upon substrate binding.

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