ArticleThe Journal of biological chemistry2013
Crystal structure and site-directed mutagenesis of 3-ketosteroid Δ1-dehydrogenase from Rhodococcus erythropolis SQ1 explain its catalytic mechanism.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 62 citations in OpenAlex.
- Rational design of a cyclohexanone dehydrogenase for enhanced α,β-desaturation and substrate specificity.Chemical science · 2024Article
- Rerouting phytosterol degradation pathway for directed androst-1,4-diene-3,17-dione microbial bioconversion.Applied microbiology and biotechnology · 2024Article
- Improving the production of 9α-hydroxy-4-androstene-3,17-dione from phytosterols by 3-ketosteroid-ΔMicrobial cell factories · 2023Article
- Structure, Mutagenesis, and QM:MM Modeling of 3-Ketosteroid ΔBiochemistry · 2023Article
- 1,2-Hydrogenation and Transhydrogenation Catalyzed by 3-Ketosteroid ΔInternational journal of molecular sciences · 2022Article
- Characterization and Degradation Pathways ofInternational journal of environmental research and public health · 2022Article
- A New 3-Ketosteroid-ΔMicroorganisms · 2022Article
- Model Setup and Procedures for Prediction of Enzyme Reaction Kinetics with QM-Only and QM:MM Approaches.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Degradation of Bile Acids by Soil and Water Bacteria.Microorganisms · 2021Review
- Universal capability of 3-ketosteroid ΔMicrobial cell factories · 2021Article
- Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols.Nutrients · 2021Review
- Structural characterization of the microbial enzyme urocanate reductase mediating imidazole propionate production.Nature communications · 2021Article
- Genetic basis for the cooperative bioactivation of plant lignans by Eggerthella lenta and other human gut bacteria.Nature microbiology · 2020Article
- The Analysis of Estrogen-Degrading and Functional Metabolism Genes inInternational journal of genomics · 2020Article
- Review
- Development of a Synthetic 3-ketosteroid ΔScientific reports · 2019Article
- Engineering of 3-ketosteroid-∆Microbial cell factories · 2018Article
- Identification, function, and application of 3-ketosteroid Δ1-dehydrogenase isozymes in Mycobacterium neoaurum DSM 1381 for the production of steroidic synthons.Microbial cell factories · 2018Article
- Article
- Site-directed mutagenesis under the direction of in silico protein docking modeling reveals the active site residues of 3-ketosteroid-ΔWorld journal of microbiology & biotechnology · 2017Article
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4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
3-Ketosteroid Δ(1)-dehydrogenases are FAD-dependent enzymes that catalyze the 1,2-desaturation of 3-ketosteroid substrates to initiate degradation of the steroid nucleus. Here we report the 2.0 Å resolution crystal structure of the 56-kDa enzyme from Rhodococcus erythropolis SQ1 (Δ(1)-KSTD1). The enzyme contains two domains: an FAD-binding domain and a catalytic domain, between which the active site is situated as evidenced by the 2.3 Å resolution structure of Δ(1)-KSTD1 in complex with the reaction product 1,4-androstadiene-3,17-dione. The active site contains four key residues: Tyr(119), Tyr(318), Tyr(487), and Gly(491). Modeling of the substrate 4-androstene-3,17-dione at the position of the product revealed its interactions with these residues and the FAD. The C1 and C2 atoms of the substrate are at reaction distance to the N5 atom of the isoalloxazine ring of FAD and the hydroxyl group of Tyr(318), respectively, whereas the C3 carbonyl group is at hydrogen bonding distance from the hydroxyl group of Tyr(487) and the backbone amide of Gly(491). Site-directed mutagenesis of the tyrosines to phenylalanines confirmed their importance for catalysis. The structural features and the kinetic properties of the mutants suggest a catalytic mechanism in which Tyr(487) and Gly(491) work in tandem to promote keto-enol tautomerization and increase the acidity of the C2 hydrogen atoms of the substrate. With assistance of Tyr(119), the general base Tyr(318) abstracts the axial β-hydrogen from C2 as a proton, whereas the FAD accepts the axial α-hydrogen from the C1 atom of the substrate as a hydride ion.
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