17Beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus: model structure and substrate specificity
T L Rizner1, J Adamski, J Stojan
1Institute of Biochemistry, Medical Faculty, University of Ljubljana, Slovenia.
Archives of Biochemistry and Biophysics
|May 23, 2001
Summary
This study models 17beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus, revealing it preferentially converts androgens over estrogens at the C17 position. Its distinct specificity differs from trihydroxynaphthalene reductase.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- 17beta-hydroxysteroid dehydrogenase (17β-HSD) is crucial for steroid hormone metabolism.
- Fungal enzymes offer unique insights into dehydrogenase activities.
- Short-chain dehydrogenase/reductase (SDR) family enzymes share conserved structural features.
Purpose of the Study:
- To structurally model and characterize 17beta-hydroxysteroid dehydrogenase from Cochliobolus lunatus.
- To elucidate substrate specificity and reaction mechanism.
- To compare its properties with related enzymes like trihydroxynaphthalene reductase.
Main Methods:
- Homology modeling using trihydroxynaphthalene reductase as a template.
- Thin-layer chromatography for substrate analysis.
- Kinetic tests to determine enzyme activity and specificity.
- Molecular modeling and dynamics for active site analysis.
Main Results:
- A homology model of fungal 17β-HSD was generated, showing high sequence identity and similar backbone trace to the template.
- The enzyme exhibits higher efficiency in converting androgens compared to estrogens, primarily at the C17 position.
- Distinct substrate specificity and inhibition patterns differentiate it from trihydroxynaphthalene reductase.
- Theorell-Chance reaction mechanism was confirmed through kinetic analysis and molecular docking.
Conclusions:
- Fungal 17β-HSD displays specific activity towards androgens.
- Structural and kinetic data provide a foundation for understanding its role in fungal steroid metabolism.
- The enzyme's distinct properties highlight the diversity within the SDR family.
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