Probing the cytochrome P-450 2B1 active site with diamantoid compounds
Jazyk angličtina Země Slovensko Médium print
Typ dokumentu časopisecké články
PubMed
8586256
Knihovny.cz E-zdroje
- MeSH
- adamantan analogy a deriváty chemie metabolismus MeSH
- aminopyrin metabolismus MeSH
- aromatické hydroxylasy * MeSH
- biofyzika MeSH
- biofyzikální jevy MeSH
- jaterní mikrozomy enzymologie MeSH
- kinetika MeSH
- kompetitivní vazba MeSH
- krysa rodu Rattus MeSH
- molekulární struktura MeSH
- potkani Wistar MeSH
- steroidhydroxylasy chemie metabolismus MeSH
- systém (enzymů) cytochromů P-450 chemie metabolismus MeSH
- techniky in vitro MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adamantan MeSH
- aminopyrin MeSH
- aromatické hydroxylasy * MeSH
- steroid 16-beta-hydroxylase MeSH Prohlížeč
- steroidhydroxylasy MeSH
- systém (enzymů) cytochromů P-450 MeSH
Hydrocarbone diamantane has been shown to be a specific substrate with a high affinity for the binding site of PB-inducible cytochrome P-450 2B1 (Hodek et al. 1988). Using a difference spectroscopy approach, a battery of diamantane analogues and diamantane oxygen containing derivatives were examined for their interaction with P-450 2B1 active site. Of the compounds (diamantane and its analogues, adamantane and triamantane) tested, diamantane had the lowest value of a spectral dissociation constant Ks = 0.5 mumol/l, indicating that diamantane was accommodated well to the cytochrome P-450 2B1, hence values of 0.46 nm and 0.66 nm for the width and length of the diamantane molecule, respectively, were used to describe of the dimensions the cytochrome P-450 binding site. Adamantane (Ks = 1.3 mumol/l) is relatively small and thus it binds loosely whereas triamantane (Ks = 4.3 mumol/l) is bulky enough to fit the binding site. This conclusion has been confirmed by spectral competition experiments as well as metabolic studies. Of all oxygen containing derivatives diamantane 1,6-dicarboxylic acid dimethylester only exhibited a pronounced ligand interaction with cytochrome P-450. Using molecular dimensions of this derivative the distance of 0.56 nm from the heme iron to the center of the substrate binding site was estimated.