ArticleThe Journal of biological chemistry2014
Substrate specificities and conformational flexibility of 3-ketosteroid 9α-hydroxylases.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
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- Production of 21-hydroxy-20-methyl-pregna-1,4-dien-3-one by modifying multiple genes in Mycolicibacterium.Applied microbiology and biotechnology · 2023Article
- Light-driven Oxidative Demethylation Reaction Catalyzed by a Rieske-type Non-heme Iron Enzyme Stc2.ACS catalysis · 2022Article
- The unusual convergence of steroid catabolic pathways inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Investigations on the Degradation of the Bile Salt Cholate via the 9,10-Microorganisms · 2021Article
- Proteome, Bioinformatic, and Functional Analyses Reveal a Distinct and Conserved Metabolic Pathway for Bile Salt Degradation in theApplied and environmental microbiology · 2021Article
- Degradation of Bile Acids by Soil and Water Bacteria.Microorganisms · 2021Review
- Efficient conversion of phytosterols into 4-androstene-3,17-dione and its C1,2-dehydrogenized and 9α-hydroxylated derivatives by engineered Mycobacteria.Microbial cell factories · 2021Article
- Expression, Purification, Refolding, and Characterization of aFrontiers in bioengineering and biotechnology · 2020Article
- A Protochlorophyllide (Pchlide)Frontiers in plant science · 2019Article
- Bacterial steroid hydroxylases: enzyme classes, their functions and comparison of their catalytic mechanisms.Applied microbiology and biotechnology · 2018Review
- New Insights on Steroid Biotechnology.Frontiers in microbiology · 2018Review
- Dioxygen activation by nonheme iron enzymes with the 2-His-1-carboxylate facial triad that generate high-valent oxoiron oxidants.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Review
- Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons.Microbial biotechnology · 2017Article
- The effect of 3-ketosteroid-Δ(1)-dehydrogenase isoenzymes on the transformation of AD to 9α-OH-AD by Rhodococcus rhodochrous DSM43269.Journal of industrial microbiology & biotechnology · 2016Article
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4 authors at 1 institution in 1 country.
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Abstract
KshA is the oxygenase component of 3-ketosteroid 9α-hydroxylase, a Rieske oxygenase involved in the bacterial degradation of steroids. Consistent with its role in bile acid catabolism, KshA1 from Rhodococcus rhodochrous DSM43269 had the highest apparent specificity (kcat/Km) for steroids with an isopropyl side chain at C17, such as 3-oxo-23,24-bisnorcholesta-1,4-diene-22-oate (1,4-BNC). By contrast, the KshA5 homolog had the highest apparent specificity for substrates with no C17 side chain (kcat/Km >10(5) s(-1) M(-1) for 4-estrendione, 5α-androstandione, and testosterone). Unexpectedly, substrates such as 4-androstene-3,17-dione (ADD) and 4-BNC displayed strong substrate inhibition (Ki S ∼100 μM). By comparison, the cholesterol-degrading KshAMtb from Mycobacterium tuberculosis had the highest specificity for CoA-thioesterified substrates. These specificities are consistent with differences in the catabolism of cholesterol and bile acids, respectively, in actinobacteria. X-ray crystallographic structures of the KshAMtb·ADD, KshA1·1,4-BNC-CoA, KshA5·ADD, and KshA5·1,4-BNC-CoA complexes revealed that the enzymes have very similar steroid-binding pockets with the substrate's C17 oriented toward the active site opening. Comparisons suggest Tyr-245 and Phe-297 are determinants of KshA1 specificity. All enzymes have a flexible 16-residue "mouth loop," which in some structures completely occluded the substrate-binding pocket from the bulk solvent. Remarkably, the catalytic iron and α-helices harboring its ligands were displaced up to 4.4 Å in the KshA5·substrate complexes as compared with substrate-free KshA, suggesting that Rieske oxygenases may have a dynamic nature similar to cytochrome P450.
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