PUBLICATION
Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase
- Authors
- Mindnich, R., and Adamski, J.
- ID
- ZDB-PUB-070504-25
- Date
- 2007
- Source
- The Journal of steroid biochemistry and molecular biology 104(3-5): 334-339 (Journal)
- Registered Authors
- Keywords
- 17Beta-hydroxysteroid dehydrogenase, Retinol dehydrogenase, Evolution, Zebrafish
- MeSH Terms
-
- 17-Hydroxysteroid Dehydrogenases/genetics
- 17-Hydroxysteroid Dehydrogenases/physiology*
- Alcohol Oxidoreductases/genetics
- Alcohol Oxidoreductases/physiology*
- Amino Acid Sequence
- Animals
- Cells, Cultured
- Humans
- Models, Molecular
- Molecular Sequence Data
- Protein Structure, Tertiary
- Retinoids/metabolism
- Sequence Alignment
- Sequence Homology, Amino Acid
- Steroids/metabolism
- Substrate Specificity
- Transfection
- Zebrafish/genetics
- PubMed
- 17467981 Full text @ Steroid Biochem. Mol. Biol.
Citation
Mindnich, R., and Adamski, J. (2007) Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase. The Journal of steroid biochemistry and molecular biology. 104(3-5):334-339.
Abstract
Determining the functional aspects of a gene or protein is a difficult and time-consuming process. De novo analysis is surely the hardest and so it is often quite useful to start with a comparison to functionally or structurally related proteins. Although 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1) can hardly be called a new protein but rather the best characterized among the family of 17beta-HSDs some aspects of structure-function relationships remain unclear. We have sought new aspects of 17beta-HSD 1 function through a comparison with its closest homolog, a photoreceptor-associated retinol dehydrogenase (prRDH). Overall amino acid identity and size of the proteins are highly conserved, but major differences occur in the C-termini, where prRDH, but not 17beta-HSD 1, harbors motifs indicative of membrane localization. To gain insight into substrate discrimination by prRDH and 17beta-HSD 1, we constructed 3D-structure models of the corresponding zebrafish enzymes. Investigation of the substrate binding site revealed a few identical amino acids, and suggested a role for G143 in zebrafish 17beta-HSD 1 and M146 and M147 in the two zebrafish paralogs prRDH 1 and prRDH 2, respectively, in substrate specificity. Activity measurements of modified proteins in transiently transfected intact HEK 293 cells hint at a putative role of these amino acids in discrimination between steroid and retinoid substrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping