Abstract
Lactoperoxidase (LPO) is an antimicrobial protein present in milk, saliva, gastric secretions, tears and upper respiratory tract secretions. LPO constitutes an important enzyme of the human immune defense system. However, LPO has also been suggested to be involved in breast cancer etiology through production of reactive free radicals and activation of carcinogenic aromatic compounds. Aromatic compounds are generally highly lipophilic and thus accumulate in highly fatty breast tissues. The aromatic compounds 4-aminobiphenyl (ABP) and 4,4'-diaminobiphenyl (BZ) are known to have carcinogenic properties. LPO catalyzes their oxidation and converts them into reactive products which bind to DNA and form adducts. These DNA adducts subsequently lead to breast cancer.
The crystal structure of LPO was obtained from Protein Data Bank. Structures of ABP and BZ were retrieved from PubChem database. Induced Fit Docking was performed using glide module from Schrodinger.
The present study reports the structural binding of ABP and BZ with LPO using in silico approaches. The amino acid residues of LPO involved in the binding with the two aromatic ligands were characterized and binding energy values were calculated.
Both ABP and BZ were placed in the substrate binding site present in the distal heme cavity of LPO with good affinity. The binding mode mimicked that of the natural substrate since these compounds did not disturb the water molecule that plays an important role in the oxidation reaction. Thus, the water molecule is potentially available for facilitating the subsequent activation of the aromatic amines to reactive species which may form DNA adducts leading to breast cancer.