Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 94, Issue 4, Pages 327-335Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2004.12.031
Keywords
17 beta-hydroxysteroid dehydrogenase type 8; modelling; three-dimensional structure; primary function; steroid dependent activity; fatty acid metabolism; polycystic kidney disease
Funding
- NIDDK NIH HHS [DK026546] Funding Source: Medline
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Significant sequence homology has been detected between prokaryotic beta-ketoacyl-[acyl carrier protein] reductases (BKR) and eukaryotic 17 beta-hydroxysteroid dehydrogenases type 8 (17 beta-HSD_8). Three-dimensional models of ternary complexes of human 17 beta-HSD_8 with NAD cofactor and two chemically distinct substrates, the BKR substrate {CH3-(CH2)(12)-CO-CH2-CO-S-[ACP]} and the HSD substrate {estradiol} have been constructed (the atomic coordinates are available on request; e-mail: pletnev@hwi.buffalo.edu). The more extensive and specific interactions of 17 beta-HSD_8 with the BKR substrate compared to interactions with estradiol raise a serious question about the enzyme's primary function in vivo and suggest that it is likely to be involved in the regulation of fatty acid metabolism rather than in the steroid-dependent activity that has been demonstrated in vitro. (c) 2005 Elsevier Ltd. All rights reserved.
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