Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Biomed Khim ; 60(5): 528-37, 2014.
Article in Russian | MEDLINE | ID: mdl-25386880

ABSTRACT

The cholesterol biosynthesis regulation is the important part of the hypercholesterolemia diseases therapy. The inhibition of the post-squalene cholesterol biosynthesis steps provide the alternative to classic statin therapy. Sterol-14a-demethylase (CYP51) is one of the hypothetical targets for it. In this work the screening of the ability to interact with human CYP51 (CYP51A1) for the nature low-weight compounds with steroid-like scaffold were performed by integration of the surface plasmon resonance biosensor and spectral titration methods. The results of the selection were 4 compounds (betulafolientriol, holothurin A, teasaponin, capsicoside A) witch had high affinity to the CYP51A1 active site. These data extend the range of compounds which may be used as specific inhibitors of CYP51 and give the permission to suggest the dynamic of the enzyme.


Subject(s)
14-alpha Demethylase Inhibitors/pharmacology , Lanosterol/pharmacology , Sterol 14-Demethylase/metabolism , 14-alpha Demethylase Inhibitors/chemistry , Humans , Lanosterol/analogs & derivatives , Lanosterol/chemistry , Protein Binding , Surface Plasmon Resonance
2.
Biokhimiia ; 61(8): 1448-59, 1996 Aug.
Article in Russian | MEDLINE | ID: mdl-8962919

ABSTRACT

Some aspects of formation and functioning of the cholesterol hydroxylase system were studied. A hybrid protein was synthesized in E. coli composed of the modified form of the (NADPH)adrenodoxin reductase precursor (N-terminal domain) and the shortened adrenodoxin precursor (C-terminal domain). The modified reductase precursor contained 12 extra amino acid residues at the N-terminus and the N-terminally shortened adrenodoxin precursor had 17 C-terminal amino acids of its targeting presequence. The hybrid reduced cytochrome P450scc in a reconstituted system. Thus, neither the extra 44 amino acids at the N-terminus of the reductase nor the 17 amino acid linker affected the interaction of the active sites in the hybrid protein. These modifications do not interfere with the binding of prosthetic groups and formation of the active sites of two enzymes in the E. coli cells. Modified N-terminal sequence of the hybrid does not affect its import into heterologous mitochondria.


Subject(s)
Adrenodoxin/biosynthesis , Enzyme Precursors/biosynthesis , Escherichia coli/metabolism , Ferredoxin-NADP Reductase/biosynthesis , Protein Precursors/biosynthesis , Adrenal Cortex/enzymology , Adrenodoxin/genetics , Amino Acid Sequence , Animals , Base Sequence , Cattle , Cholesterol Side-Chain Cleavage Enzyme/biosynthesis , Cholesterol Side-Chain Cleavage Enzyme/genetics , DNA, Recombinant , Enzyme Precursors/genetics , Escherichia coli/genetics , Ferredoxin-NADP Reductase/genetics , Mitochondria/enzymology , Molecular Sequence Data , Plasmids , Protein Precursors/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...