Abstract |
Seventeen missense mutations of 25-hydroxyvitamin D(3) 1alpha-hydroxylase ( CYP27B1) that cause Vitamin D-dependent rickets type I (VDDR-I) have been identified. To understand the mechanism by which each mutation disrupts 1alpha-hydroxylase activity and to visualize the substrate-binding site, we performed the homology modeling of CYP27B1. The three-dimensional (3D) structure of CYP27B1 was modeled on the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray structure of a eukaryotic CYP. The 3D structure of CYP27B1 contains 17 helices and 6 beta-strands, and the overall structural folding is similar to the available structures of soluble CYPs as well as to the template CYP2C5. Mapping of the residues responsible for VDDR-I has provided much information concerning the function of each mutant. We have previously reported site-directed mutagenesis studies on several mutants of CYP27B1 causing VDDR-1, and suggested the role of each residue. All these suggestions are in good agreement with our 3D-model of CYP27B1. Furthermore, this model enabled us to predict the function of the other mutation residues responsible for VDDR-I.
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Authors | Keiko Yamamoto, Hiroyuki Masuno, Natsumi Sawada, Toshiyuki Sakaki, Kuniyo Inouye, Masaji Ishiguro, Sachiko Yamada |
Journal | The Journal of steroid biochemistry and molecular biology
(J Steroid Biochem Mol Biol)
Vol. 89-90
Issue 1-5
Pg. 167-71
(May 2004)
ISSN: 0960-0760 [Print] England |
PMID | 15225767
(Publication Type: Journal Article)
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Chemical References |
- Cytochrome P-450 Enzyme System
- CYP2C5 protein, Oryctolagus cuniculus
- Cytochrome P450 Family 2
- Steroid 21-Hydroxylase
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
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Topics |
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
(chemistry)
- Amino Acid Sequence
- Animals
- Crystallography, X-Ray
- Cytochrome P-450 Enzyme System
(chemistry)
- Cytochrome P450 Family 2
- Humans
- Models, Molecular
- Molecular Sequence Data
- Protein Conformation
- Rabbits
- Sequence Homology, Amino Acid
- Steroid 21-Hydroxylase
(chemistry)
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