title: A molecular model of human Lysyl Oxidase (LOX) with optimal copper orientation in the catalytic cavity for induced fit docking studies with potential modulators.
abstract: Lysyl oxidase (LOX) is a copper dependent amine oxidase which catalyses the cross linking of collagen and elastin towards the maturation of extracellular matrix. The expression and activity of LOX is known to vary under pathological conditions such as tumorigenesis, hyperhomocysteinemia, copper deficiency diseases, pseudoexfoliation syndrome and proliferative diabetic retinopathy. Despite the implication of LOX in many diseases, there is inadequate information about its structure. Therefore, we describe a molecular model of Human Lysyl Oxidase (LOX) with optimal copper orientation in the catalytic cavity for induced fit docking studies with potential modulators. The predicted model was found to be highly plausible as per the stereochemistry checks. Further, Molecular Dynamics (MD) studies also inferred the stability of the predicted structure. We performed Induced Fit Docking (IFD) of LOX modulators to the predicted structure and also validated the molecular interactions in implicit solvent model by calculating Molecular Mechanics Generalized Born Surface Area (MMGBSA). The IFD results strongly reveal that aspartic acid residues in the catalytic cavity as the key players in establishing interactions with small molecules. The insights from this study will aid in better exploration of the structure-function relationship of LOX.
authors.affiliation: R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India ; Dept. of Biological Sciences, Birla Institute of Technology and Science, Pilani (Rajasthan), India.
authors.forename: Renganathan
authors.initials: R
authors.lastname: Bhuvanasundar
authors.affiliation: Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya Chennai, India ; Dept. of Biological Sciences, Birla Institute of Technology and Science, Pilani (Rajasthan), India.
authors.forename: Arun
authors.initials: A
authors.lastname: John
authors.affiliation: R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Konerirajapuram Natarajan
authors.initials: KN
authors.lastname: Sulochana
authors.affiliation: R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India.
authors.forename: Karunakaran
authors.initials: K
authors.lastname: Coral
authors.affiliation: Dept. of Biological Sciences, Birla Institute of Technology and Science, Pilani (Rajasthan), India.
authors.forename: Perinkulam Ravi
authors.initials: PR
authors.lastname: Deepa
authors.affiliation: Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya Chennai, India.
authors.forename: Vetrivel
authors.initials: V
authors.lastname: Umashankar
keywords: Copper ion; Induced Fit Docking; Lysyl Oxidase; Modelling; Molecular dynamics