Rational proteomics IV: modeling the primary function of the mammalian 17beta-hydroxysteroid dehydrogenase type 8.
Significant sequence homology has been detected between prokaryotic beta-ketoacyl-[acyl carrier protein] reductases (BKR) and eukaryotic 17beta-hydroxysteroid dehydrogenases type 8 (17beta-HSD_8). Three-dimensional models of ternary complexes of human 17beta-HSD_8 with NAD cofactor and two chemically distinct substrates, the BKR substrate {CH3-(CH2)(12)-CO-CH(2)-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 17beta-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.
Pletnev
Vladimir Z
VZ
Department of Structural Biology, Hauptman-Woodward Medical Research Institute, SUNY at Buffalo, NY 14203, USA. pletnev@hwi.buffalo.edu
Duax
William L
WL
D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase; D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D029688:Brassica napus; D019295:Computational Biology; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D016415:Sequence Alignment; D013379:Substrate Specificity
C102228:HSD17B8 protein, human; D007527:Isoenzymes; D011506:Proteins; D009243:NAD; D004958:Estradiol; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase