3C6G

Crystal structure of CYP2R1 in complex with vitamin D3

「2OJD」から置き換えられました

3C6G の概要

• エントリーDOI: 10.2210/pdb3c6g/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900012
• 分子名称: Cytochrome P450 2R1, Cycloheptakis-(1-4)-(alpha-D-glucopyranose), UNKNOWN ATOM OR ION, ... (6 entities in total)
• 機能のキーワード: cytochrome p450, vitamin d3, vitamin d 25-hydroxylase, drug metabolism, structural genomics, structural genomics consortium, sgc, disease mutation, endoplasmic reticulum, heme, iron, membrane, metal-binding, microsome, monooxygenase, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114590.78

構造登録者

Strushkevich, N.V.,Min, J.,Loppnau, P.,Tempel, W.,Arrowsmith, C.H.,Edwards, A.M.,Sundstrom, M.,Weigelt, J.,Bochkarev, A.,Plotnikov, A.N.,Park, H.,Structural Genomics Consortium (SGC) (登録日: 2008-02-04, 公開日: 2008-02-19, 最終更新日: 2023-08-30)

主引用文献

Strushkevich, N.,Usanov, S.A.,Plotnikov, A.N.,Jones, G.,Park, H.W.
Structural analysis of CYP2R1 in complex with vitamin D3.
J.Mol.Biol., 380:95-106, 2008

PubMed Abstract: The activation of vitamin D to its hormonal form is mediated by cytochrome P450 enzymes. CYP2R1 catalyzes the initial step converting vitamin D into 25-hydroxyvitamin D. A CYP2R1 gene mutation causes an inherited form of rickets due to 25-hydroxylase deficiency. To understand the narrow substrate specificity of CYP2R1 we obtained the hemeprotein in a highly purified state, confirmed the enzyme as a vitamin D 25-hydroxylase, and solved the crystal structure of CYP2R1 in complex with vitamin D3. The CYP2R1 structure adopts a closed conformation with the substrate access channel being covered by the ordered B'-helix and slightly opened to the surface, which defines the substrate entrance point. The active site is lined by conserved, mostly hydrophobic residues. Vitamin D3 is bound in an elongated conformation with the aliphatic side-chain pointing toward the heme. The structure reveals the secosteroid binding mode in an extended active site and allows rationalization of the molecular basis of the inherited rickets associated with CYP2R1.

PubMed: 18511070
DOI: 10.1016/j.jmb.2008.03.065

実験手法

X-RAY DIFFRACTION (2.8 Å)