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

被引:20
作者
Bhuvanasundar, Renganathan [1 ,3 ]
John, Arun [2 ,3 ]
Sulochana, Konerirajapuram Natarajan [1 ]
Coral, Karunakaran [1 ]
Deepa, Perinkulam Ravi [3 ]
Umashankar, Vetrivel [2 ]
机构
[1] Sankara Nethralaya, RS Mehta Jain Dept Biochem & Cell Biol, Vis Res Fdn, Madras, Tamil Nadu, India
[2] Sankara Nethralaya, Ctr Bioinformat, Vis Res Fdn, Madras, Tamil Nadu, India
[3] Birla Inst Technol & Sci, Dept Biol Sci, Pilani, Rajasthan, India
关键词
Lysyl Oxidase; Copper ion; Modelling; Molecular dynamics; Induced Fit Docking;
D O I
10.6026/97320630010406
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:406 / 412
页数:7
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