9BAT
Crystal structure of sterol 14 alpha-demethylase (CYP51) from deep-sea fish Coryphaenoides armatus (abyssal grenadier) in the ligand-free state
Summary for 9BAT
| Entry DOI | 10.2210/pdb9bat/pdb |
| Descriptor | Lanosterol 14-alpha demethylase, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total) |
| Functional Keywords | monooxygenase, cytochrome p450, endoplasmic reticulum, sterol biosynthesis, oxidoreductase |
| Biological source | Coryphaenoides armatus |
| Total number of polymer chains | 2 |
| Total formula weight | 103306.09 |
| Authors | Hargrove, T.Y.,Wawrzak, Z.,Minasov, G.,Lepesheva, G.I. (deposition date: 2024-04-04, release date: 2025-06-25, Last modification date: 2025-07-09) |
| Primary citation | Hargrove, T.Y.,Lamb, D.C.,Wawrzak, Z.,Minasov, G.,Goldstone, J.V.,Kelly, S.L.,Stegeman, J.J.,Lepesheva, G.I. Unique Structural Features Relate to Evolutionary Adaptation of Cytochrome P450 in the Abyssal Zone. Int J Mol Sci, 26:-, 2025 Cited by PubMed Abstract: Cytochromes P450 (CYPs) form one of the largest enzyme superfamilies, with similar structural folds yet biological functions varying from synthesis of physiologically essential compounds to metabolism of myriad xenobiotics. Sterol 14α-demethylases (CYP51s) represent a very special P450 family, regarded as a possible evolutionary progenitor for all currently existing P450s. In metazoans CYP51 is critical for the biosynthesis of sterols including cholesterol. Here we determined the crystal structures of ligand-free CYP51s from the abyssal fish and human-. Comparative sequence-structure-function analysis revealed specific structural elements that imply elevated conformational flexibility, uncovering a molecular basis for faster catalytic rates, lower substrate selectivity, and intrinsic resistance to inhibition. In addition, the structure displayed a large-scale repositioning of structural segments that, in vivo, are immersed in the endoplasmic reticulum membrane and border the substrate entrance (the FG arm, >20 Å, and the β4 hairpin, >15 Å). The structural distinction of CYP51, which is the first structurally characterized deep sea P450, suggests stronger involvement of the membrane environment in regulation of the enzyme function. We interpret this as a co-adaptation of the membrane protein structure with membrane lipid composition during evolutionary incursion to life in the deep sea. PubMed: 40565153DOI: 10.3390/ijms26125689 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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