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Introduction

Rickets is a disease caused by a vitamin D deficiency. Vitamin D can be obtained from ultra violet radiation and from various food sources. Cytochrome P450 enzymes are involved in the first step to regulate and process vitamin D in the human body.

Overall Structure

Cytochrome P450 exists as an asymmetric dimer. Each dimeric unit contains 12 α-helices (labeled A-L) along with β-sheets, which are mostly located on one side of the molecule. Helices F and G form the dimeric interface of cytochrome P450, and are also involved in the formation of the active site. The dimeric interface of the protein is stabilized by electrostatic interactions between the C terminus of the G helix of one molecule (Arg259 and Asp255) with the N terminus residues of the F helix of the second molecule (Asp206 and His209) and vice versa. Two molecules of 2-hydroxypropyl-β-cyclodextrin, which is used to dissolve vitamin D3, are also found near the dimer interface.

Binding Interactions

The binding of Vitamin D3 occurs in a channel between the G and I helices and B' helix and B-C loop. In the you can see the residues that interact to bind Vitamin D3 and the channel between. Most of these residues are hydrophobic and thus have non polar interactions. Binding of the substrate causes the access channel to close. The B' helix has a flexible C terminus and can adopt a helix or loop conformation, which has van der waal interactions with the F-G loop. The B' helix unwinds outward to allow entrance of the substrate into the active site channel. CYP2R1 has an extended binding site where the access channel is part of the active site. -catalyzes initial step for converting vitamin D into 25-hydroxyvitamin D -mutation causes rickets-25-hydroxylase deficiency

Additional Features

This molecule has a heme which is bound to iron, which, combined with its structural conformation, allows for hydroxylation with the attached substrate. This molecule carries out important functions and is not species or sex specific.

Quiz Question 1

(merely an example of what this section might look like)

rom can you identify the green, red, and blue parts of the molecule?

See Also

• Cytochrome P450
• Drug Metabolism by CYP450 Enzymes
• 3w0y
• 3w0c

Credits

Introduction - Sami Kriksceonaitis

Overall Structure - Kati Johnson

Drug Binding Site - Isabel Hand

Additional Features - Elizabeth Humble

Quiz Question 1 - Matthew Tiller1

References

1. ↑ Strushkevich N, Usanov SA, Plotnikov AN, Jones G, Park HW. Structural analysis of CYP2R1 in complex with vitamin D3. J Mol Biol. 2008 Jun 27;380(1):95-106. Epub 2008 Apr 8. PMID:18511070 doi:10.1016/j.jmb.2008.03.065