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K267Q
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participation in electrostatic interaction of P-450scc with adrenodoxin
K338Q
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removed from heme group but still very important for interaction with adrenodoxin, K helix
K342Q
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removed from heme group but still very important for interaction with adrenodoxin, K helix
R425Q
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most harmful substitution, L helix, heme-binding region
R425Q/R426C
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double mutant, most harmful substitution
R425Q/R426Q
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double mutant, most harmful substitution
c835delA
a naturally occuring CYP11A1 frameshift mutation, heterozygous mutant, phenotype, overview
L141W
a naturally occuring CYP11A1 missense mutation, heterozygous mutant, phenotype, overview
V415E
a naturally occuring CYP11A1 missense mutation, heterozygous mutant, phenotype, overview
K103Q
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decrease of stability
K103Q
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expression similar to wild-type, decreased stability or an altered heme or substrate pocket, B'-C loop, no change in interaction of P-450scc and adrenodoxin
K104Q
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dramatic decrease in expression level
K104Q
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decreased expression, B'-C loop, no change in interaction of P-450scc and adrenodoxin
K109Q
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dramatic changes in folding and heme insertion
K109Q
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change in folding, thus, an inability of heme to be retained, helix C, no change in interaction of P-450scc and adrenodoxin
K110Q
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folding and heme insertion not affected
K110Q
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expression similar to wild-type, helix C, does not appear to play a role in adrenodoxin binding because it shows no change in interaction of P-450scc and adrenodoxin
K145Q
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K145Q
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expression similar to wild-type, helix D
K148Q
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expression level is not affected, extreme instable and rapid denaturation
K148Q
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extremely unstable, helix D
K394Q
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functional parameters decreased because substitution is close to 405 position, but to much lower extend
K394Q
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expression similar to wild-type, "meander", involved in the interaction of P-450scc with its electron-transfer partners
K403Q
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participation in electrostatic interaction of P-450scc with adrenodoxin
K403Q
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functional parameters decreased because substitution is close to 405 position, but to much lower extend, shows importance of this residue for electrostatic interaction with negatively charged residues of ferredoxin
K403Q
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expression similar to wild-type, located between the meander and the heme-binding region, important role in electrostatic interactions with adrenodoxin, ability to bind adrenodoxin affected to lower extent than K405Q
K405Q
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participation in electrostatic interaction of P-450scc with adrenodoxin
K405Q
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dramatic loss of activity, shows importance of this residue for electrostatic interaction with negatively charged residues of ferredoxin
K405Q
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expression similar to wild-type, 4fold decrease in efficiency of enzymatic reduction by adrenodoxin and adrenodoxin reductase, and a 3.3fold decrease of cholesterol side chain cleavage activity, located between the meander and the heme-binding region, important role in electrostatic interactions with adrenodoxin
R426Q
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participation in electrostatic interaction of P-450scc with adrenodoxin
R426Q
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expression similar to wild-type, serious changes in proteine folding and ability to insert and bind heme correctly, unable to catalyze cholesterol side chain cleavage reaction, although it is able to bind cholesterol, L helix, heme-binding region, important role in electrostatic interactions with adrenodoxin
additional information
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site-directed mutagenesis, no evident changes in functional properties for KQ mutants, 103, 110, 145, 394 and 403 with activities between 69 and 86% of wild-type
additional information
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site directed mutagenesis. complex stabilizing salt bridges: K403 of P-450scc with D76 of adrenodoxin, K405 with D72, R426 with E73 and K267 with E47, multiple electrostatic interactions between the negatively charged residues of adrenodoxin and positively charged groups of P-450scc
additional information
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construction of fusion proteins of enzyme plus adrenodoxin plus adrenodoxin reductase, fusion in order enzyme - adrenodoxin - adrenodoxin reductase gives 30-fold higher enzymatic activity than fusion in same order with human enzyme and 14-fold higher activity than fusion with human enzyme in order adrenodoxin reductase adrenodoxin enzyme. CO-difference spectra do not show the presence of a normally folded enzyme moiety
additional information
construction of a fusion protein consisting of cytochrome P450scc (CYP11A1), adrenodoxin and adrenodoxin reductase including 2A peptide from Picornaviridae which is capable of self-cleavage. Introduction to Escherichia coli leads to a high level of expression but no cleavage. In yeast Saccharomyces cerevisiae, the discrete proteins P450scc-2A, adrenodoxin-2A and adrenodoxin reductase are expressed, with a significant proportion present in a fusion adrenodoxin-2A-adrenodoxin reductase. The enzyme system is catalytically active
additional information
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construction of a fusion protein consisting of cytochrome P450scc (CYP11A1), adrenodoxin and adrenodoxin reductase including 2A peptide from Picornaviridae which is capable of self-cleavage. Introduction to Escherichia coli leads to a high level of expression but no cleavage. In yeast Saccharomyces cerevisiae, the discrete proteins P450scc-2A, adrenodoxin-2A and adrenodoxin reductase are expressed, with a significant proportion present in a fusion adrenodoxin-2A-adrenodoxin reductase. The enzyme system is catalytically active
additional information
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construction of fusion proteins of enzyme plus adrenodoxin plus adrenodoxin reductase, fusion in order bovine enzyme - adrenodoxin - adrenodoxin reductase gives 30-fold higher enzymatic activity than fusion in same order with human enzyme and 14-fold higher activity than fusion with human enzyme in order adrenodoxin reductase adrenodoxin enzyme. Dimers of enzyme with adrenodoxin in order enzyme adrenodoxin or adrenodoxin enzyme show minimal side chain cleavage activity. CO difference spectra reveal a denatured cytochrome P450 in dimer fusion proteins
additional information
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mutation of a cysteine residue in the F-G loop leads to altered membrane interaction and activity
additional information
mutation of CYP11A1 leads to individuals with 46,XY disorders of sex development and primary adrenal failure, identification of P450scc mutations in children, analysis of genotype/phenotype correlations, overview
additional information
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mutation of CYP11A1 leads to individuals with 46,XY disorders of sex development and primary adrenal failure, identification of P450scc mutations in children, analysis of genotype/phenotype correlations, overview