3E5K

Crystal structure of CYP105P1 wild-type 4-phenylimidazole complex

Summary for 3E5K

• Entry DOI: 10.2210/pdb3e5k/pdb
• Related: 3E5J 3E5L
• Descriptor: Cytochrome P450 (Cytochrome P450 hydroxylase), PROTOPORPHYRIN IX CONTAINING FE, 4-PHENYL-1H-IMIDAZOLE, ... (4 entities in total)
• Functional Keywords: p450, oxidoreductase, heme, iron, metal-binding, monooxygenase
• Biological source: Streptomyces avermitilis
• Total number of polymer chains: 1
• Total formula weight: 45172.12

Authors

Xu, L.H.,Fushinobu, S.,Ikeda, H.,Wakagi, T.,Shoun, H. (deposition date: 2008-08-14, release date: 2008-12-30, Last modification date: 2023-11-01)

Primary citation

Xu, L.H.,Fushinobu, S.,Ikeda, H.,Wakagi, T.,Shoun, H.
Crystal structures of cytochrome P450 105P1 from Streptomyces avermitilis: conformational flexibility and histidine ligation state
J.Bacteriol., 191:1211-1219, 2009

PubMed Abstract: The polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway of Streptomyces avermitilis contains two position-specific hydroxylases, C26-specific CYP105P1 and C1'-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-bound wild-type (WT-4PI), and ligand-free H72A mutant (H72A-free) forms. The BC loop region in the WT-free structure has a unique feature; the side chain of His72 within this region is ligated to the heme iron. On the other hand, this region is highly disordered and widely open in WT-4PI and H72A-free structures, respectively. Histidine ligation of wild-type CYP105P1 was not detectable in solution, and a type II spectral change was clearly observed when 4-phenylimidazole was titrated. The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein. In the H72A-free structure, there is a large pocket that is of the same size as the filipin molecule. The highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate.

PubMed: 19074393
DOI: 10.1128/JB.01276-08

Experimental method

X-RAY DIFFRACTION (2.6 Å)