Homology model of 1α,25-dihydroxyvitamin D3 24-hydroxylase cytochrome P450 24A1 (CYP24A1): Active site architecture and ligand binding

Gomaa, Mohamed Sayed, Simons, Claire ORCID: https://orcid.org/0000-0002-9487-1100 and Brancale, Andrea ORCID: https://orcid.org/0000-0002-9728-3419 2007. Homology model of 1α,25-dihydroxyvitamin D3 24-hydroxylase cytochrome P450 24A1 (CYP24A1): Active site architecture and ligand binding. The Journal of Steroid Biochemistry and Molecular Biology 104 (1-2) , pp. 53-60. 10.1016/j.jsbmb.2006.09.041

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Abstract

Homology models of cytochrome P450 24A1 (CYP24A1) were constructed using three human P450 structures, CYP2C8, CYP2C9 and CYP3A4 as templates for the model building. Using molecular operating environment (MOE) software the lowest energy CYP24A1 model was then assessed for stereochemical quality and side chain environment. Further active site optimisation of the CYP24A1 model built using the CYP3A4 template was performed by molecular dynamics to generate a final CYP24A1 model. The natural substrate, 1,25-dihydroxyvitamin D3 (calcitriol) and the CYP24 inhibitor (R)-N-(2-(1H-imidazol-1-yl)-2-phenylethyl)-4′-chlorobiphenyl-4-carboxamide ((R)-VID-400) were docked into the model allowing further validation of the active site architecture. Using the docking studies structurally and functionally important residues were identified with subsequent characterisation of secondary structure.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords:	CYP24; Homology model; MOE; 1,25-Dihydroxyvitamin D3; Docking studies; Inhibitor interactions
Publisher:	Elsevier
ISSN:	0960-0760
Last Modified:	05 Jan 2024 06:01
URI:	https://orca.cardiff.ac.uk/id/eprint/970

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