Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s.
The interaction of adrenodoxin (Adx) and NADPH cytochrome P450 reductase (CPR) with human microsomal steroidogenic cytochrome P450s was studied. It is found that Adx, mitochondrial electron transfer protein, is able to support reactions catalyzed by human microsomal P450s: full length CYP17, truncated CYP17, and truncated CYP21. CPR, but not Adx, supports activity of truncated CYP19. Truncated and the full length CYP17s show distinct preference for electron donor proteins. Truncated CYP17 has higher activity with Adx compared to CPR. The alteration in preference to electron donor does not change product profile for truncated enzymes. The electrostatic contacts play a major role in the interaction of truncated CYP17 with either CPR or Adx. Similarly electrostatic contacts are predominant in the interaction of full length CYP17 with Adx. We speculate that Adx might serve as an alternative electron donor for CYP17 at the conditions of CPR deficiency in human.
Pechurskaya
Tatiana A
TA
Institute of Bioorganic Chemistry, Academy of Sciences of Belarus, Kuprevicha st., 5/2, Minsk 220141, Belarus.
Harnastai
Ivan N
IN
Grabovec
Irina P
IP
Gilep
Andrei A
AA
Usanov
Sergey A
SA
D000325:Adrenodoxin / Q000378:metabolism*; D000595:Amino Acid Sequence; D001141:Aromatase / Q000378:metabolism*; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D016415:Sequence Alignment; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism*
D000325:Adrenodoxin; D001141:Aromatase; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D005287:Ferredoxin-NADP Reductase; D009251:NADPH-Ferrihemoprotein Reductase