A molecular model of human Lysyl Oxidase (LOX) with optimal copper orientation in the catalytic cavity for induced fit docking studies with potential modulators

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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
Authors	Renganathan Bhuvanasundar^1,3, Arun John^2,3, Konerirajapuram Natarajan Sulochana¹, Karunakaran Coral¹, Perinkulam Ravi Deepa³ & Vetrivel Umashankar²*
Affiliation	¹R.S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Sankara Nethralaya, Chennai, India; ²Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya Chennai, India; 3Dept. of Biological Sciences, Birla Institute of Technology and Science, Pilani (Rajasthan), India
Email	vumashankar@gmail.com; *Corresponding author
Article Type	Hypothesis
Date	Received June 12, 2014; Revised June 27, 2014; Accepted June 27, 2014; Published July 22, 2014
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.
Keywords	Lysyl Oxidase, Copper ion, Modelling, Molecular dynamics, Induced Fit Docking.
Citation	Bhuvanasundar et al. Bioinformation 10(7): 406-412 (2014)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.