Homology modeling of human 25-hydroxyvitamin D3 1alpha-hydroxylase (CYP27B1) based on the crystal structure of rabbit CYP2C5.

  • Yamamoto K
  • Masuno H
  • Sawada N
 et al. 
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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.

Author-supplied keywords

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase: chemistr
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 Enzyme System: chemistry
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Rabbits
  • Sequence Homology, Amino Acid
  • Steroid 21-Hydroxylase
  • Steroid 21-Hydroxylase: chemistry

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  • Keiko Yamamoto

  • Hiroyuki Masuno

  • Natsumi Sawada

  • Toshiyuki Sakaki

  • Kuniyo Inouye

  • Masaji Ishiguro

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