1X8V
Estriol-bound and ligand-free structures of sterol 14alpha-demethylase (CYP51)
Summary for 1X8V
| Entry DOI | 10.2210/pdb1x8v/pdb |
| Related | 1E9X 1EA1 1H5Z 1U13 |
| Descriptor | Cytochrome P450 51, PROTOPORPHYRIN IX CONTAINING FE, ESTRIOL, ... (4 entities in total) |
| Functional Keywords | alpha-beta, heme co-factor, protein-estriol complex, oxidoreductase |
| Biological source | Mycobacterium tuberculosis |
| Cellular location | Cytoplasm: P0A512 |
| Total number of polymer chains | 1 |
| Total formula weight | 52670.53 |
| Authors | Podust, L.M.,Yermalitskaya, L.V.,Lepesheva, G.I.,Podust, V.N.,Dalmasso, E.A.,Waterman, M.R. (deposition date: 2004-08-18, release date: 2004-11-23, Last modification date: 2023-08-23) |
| Primary citation | Podust, L.M.,Yermalitskaya, L.V.,Lepesheva, G.I.,Podust, V.N.,Dalmasso, E.A.,Waterman, M.R. Estriol Bound and Ligand-free Structures of Sterol 14alpha-Demethylase. Structure, 12:1937-1945, 2004 Cited by PubMed Abstract: Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes and drug targets in antifungal therapy. Here, we report CYP51 structures in ligand-free and estriol bound forms. Using estriol as a probe, we determined orientation of the substrate in the active site, elucidated protein contacts with the invariant 3beta-hydroxy group of a sterol, and identified F78 as a key discriminator between 4alpha-methylated and 4alpha,beta-dimethylated substrates. Analysis of CYP51 dynamics revealed that the C helix undergoes helix-coil transition upon binding and dissociation of a ligand. Loss of helical structure of the C helix in the ligand-free form results in an unprecedented opening of the substrate binding site. Upon binding of estriol, the BC loop loses contacts with molecular surface and tends to adopt a closed conformation. A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics. PubMed: 15530358DOI: 10.1016/j.str.2004.08.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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