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Mindnich, R. ; Adamski, J.

Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase.

J. Steroid Biochem. Mol. Biol. 104, 334-339 (2007)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 17Beta-hydroxysteroid dehydrogenase; Retinol dehydrogenase; Evolution; Zebrafish
ISSN (print) / ISBN 0960-0760
e-ISSN 0960-0760
Zeitschrift Journal of Steroid Biochemistry and Molecular Biology, The
Quellenangaben Band: 104, Heft: 3-5, Seiten: 334-339 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Molekulare Endokrinologie und Metabolismus (MEM)