9ONH
Structure of ancestral-reconstructed cytochrome P450 11A1 (CYP11A1) in complex with desmosterol
Summary for 9ONH
| Entry DOI | 10.2210/pdb9onh/pdb |
| Descriptor | Ancestral Cytochrome P450 11A1 (CYP11A1), PROTOPORPHYRIN IX CONTAINING FE, desmosterol (3 entities in total) |
| Functional Keywords | cytochrome p450, steroidogenesis, evolution, oxidoreductase |
| Biological source | synthetic construct |
| Total number of polymer chains | 1 |
| Total formula weight | 57351.93 |
| Authors | |
| Primary citation | Chagas, B.C.A.,Brixius, B.,Wang, P.C.,Pirhadi, S.,Aziz, O.,Koes, D.R.,Gillam, E.M.J.,Bernhardt, R.,Brixius-Anderko, S. How evolution shaped the structure of steroidogenic cytochrome P450 11A. J.Inorg.Biochem., 274:113105-113105, 2025 Cited by PubMed Abstract: The cytochrome P450 enzyme 11A1 (CYP11A1) is the most important player in steroid hormone biosynthesis, catalysing the first and rate-limiting step, the side-chain cleavage of cholesterol to pregnenolone, which provides the precursor for all major steroid hormones. A resurrected ancestral isoform of CYP11A (CYP11A_N1) exhibits different substrate specificities to extant vertebrate CYP11A1 forms which implies an evolutionary change in structural features. Hence, we solved the structure of the resurrected ancestral CYP11A_N1 isoform and identified the major structural changes between ancestral and extant CYP11A isoforms that lead to different catalytic properties for cholesterol metabolism. Our work presents the first structure of an ancestral mitochondrial cytochrome P450 and highlights how structural changes shaped the evolution of steroid hormone biosynthesis. PubMed: 41075759DOI: 10.1016/j.jinorgbio.2025.113105 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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