Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1alpha,25-(OH)2D3-26,23-lactone.

ABSTRACT: Studies of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24A1) have demonstrated that it is a bifunctional enzyme capable of the 24-hydroxylation of 1alpha,25-(OH)(2)D(3), leading to the excretory form, calcitroic acid, and 23-hydroxylation, culminating in 1alpha,25-(OH)(2)D(3)-26,23-lactone. The degree to which CYP24A1 performs either 23- or 24-hydroxylation is species-dependent. In this paper, we show that the human enzyme that predominantly 24-hydroxylates its substrate differs from the opossum enzyme that 23-hydroxylates it at only a limited number of amino acid residues. Mutagenesis of the human form at a single substrate-binding residue (A326G) dramatically changes the regioselectivity of the enzyme from a 24-hydroxylase to a 23-hydroxylase, whereas other modifications have no effect. Al

SUBMITTER: Prosser DE 

PROVIDER: S-EPMC1937525 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature