Chemical modification of adrenocortical cytochrome P-450scc with tetranitromethane.
Selective chemical modification of adrenocortical cytochrome P-450scc, responsible for key stages of steroid biogenesis, with tetranitromethane has been carried out. Nitration of the cytochrome P-450scc tyrosine residues results in heme protein inactivation with syncatalytic loss of enzyme activity. Analysis of the cytochrome P-450scc inactivation kinetics indicates that there are several pools of tyrosine residues, differing in their accessibility to tetranitromethane. The modification of cytochrome P-450scc results in changes in the hemeprotein spectral properties and its conformation which indicates to the involvement of essential tyrosine residue(s) in the heme-protein interaction. Cholesterol and adrenodoxin (high-spin effectors) prevent the inactivation of cytochrome P-450scc with tetranitromethane, i.e., protect the essential tyrosine residue(s) from modification. Possible functions of the tyrosine residues in the cytochrome P-450scc molecule are discussed.
D000302:Adrenal Cortex / Q000201:enzymology*; D000325:Adrenodoxin / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000494:pharmacology; D002942:Circular Dichroism; D003577:Cytochrome P-450 Enzyme System; D008697:Methane / Q000031:analogs & derivatives; D010446:Peptide Fragments / Q000032:analysis; D011487:Protein Conformation; D013057:Spectrum Analysis; D013774:Tetranitromethane; D014443:Tyrosine
D010446:Peptide Fragments; D000325:Adrenodoxin; D014443:Tyrosine; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013774:Tetranitromethane; D008697:Methane