Bioinformatics

Cytochromes P450 (CYP) which are a superfamily of heme containing enzymes play an important role in detoxification and metabolic activation and which generally monooxygenate hydrophobic compounds. The human cytochrome P450 4F22 (CYP4F22) was categorized

...

into “orphan” CYPs because of its unknown function. CYP4F22 is a potential drug target for cancer therapy. However, three-dimensional structure, the active site topology and substrate specificity of CYP4F22 remain unclear. In this study, a three-dimensional model of human P450 4F22 was constructed by comparative modeling using Modeller 9v5. The resulting model was refined by energy minimization, subjected to the quality assessment from both geometric and energetic aspects and was found to be of reasonable quality. Docking approach was employed to dock arachidonic acid into the active site of CYP4F22 in order to probe the ligand-binding modes. As a result, several key residues were identified to be responsible for the binding of arachidonic acid with CYP4F22. These findings provide useful information for understanding the biological roles of CYP4F22 and structure-based drug design.

It was recently found that CYP4F22 was specifically expressed in human breast cancer tissues. For this reason, human CYP4F22 has been suggested to be a potential drug target for cancer therapy. However, to date, information regarding the structure and ligand binding site is not available for CYP4F22 and hence structural information might help us to understand the ligand interaction.

Authors: Suresh Kumar.

Source: www.bioinformation.net volume 7(4): 207-210 (2011).

Publication date: October 14, 2011.

Figure : (a) Ribbon schematic representation of the homology model of CYP4F22. The heme is shown in the center of the figure in red stick. Various visible regions of secondary structure elements are labeled in the figure, (b) Predicted active sites of CYP4F22, (c) 2D structure of arachidonic acid and (d) a close view of CYP4F22 with arachidonic acid. Key residues are shown in red spheres and labeled. The substrate arachidonic acid is shown as grey stick.

Source: http://www.bioinformation.net/007/97320630007207.pdf