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Structural and Putative Functional Role of Conserved Water Molecular Cluster in the X-ray Structures of Plant Thiol Proteases: A Molecular Dynamics Simulation Study

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Abstract

Cysteine proteases are involved in the osteoporosis, arthritis, cancer metastasis and protein degrading related diseases. Role of water molecules in the catalytic mechanism of cysteine proteases are uniquely important. So for searching the detail role of H-bonded water cluster in plant thiol proteases, we have analyzed 21 X-ray and solvated structures and performed 10 ns MD-simulation of their apo and ligand bound forms. Molecular dynamics simulation study was employed at 300 K by NAMD program. The results have shown the presence of a conserved water molecular cluster containing six hydrophilic centers (W1–W6). During the simulation, water molecular network adopts two types of H-bonding patterns in the enzyme. Some of the conserved water molecules of the cluster (Type-I and II) interact with the residues of S2 and S3 subsites and may stabilize the active center of the plant cysteine proteases. Detail analysis of ASA, interaction energy and torsion angles of the subsite residues have indicated the possibility of involvement of this water cluster to ligand binding process of the enzyme. However, the simulation results indicate the occupancy of Type-I topology (of the H-bonding network/cluster of water molecules) is higher than Type-II in the ligand bound form.

Graphical Abstract

The six conserved H-bonded water molecules are interact to S2 and S3 subsites and may influence the ligand binding process of Plant Thiol Proteases.

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Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology, Durgapur, 713 209, India

    Tapas K. Nandi, Hridoy R. Bairagya, Deepak K. Mishra, Bishnu P. Mukhopadhyay & Avik Banerjee

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  1. Tapas K. Nandi
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  2. Hridoy R. Bairagya
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  3. Deepak K. Mishra
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  4. Bishnu P. Mukhopadhyay
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  5. Avik Banerjee
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Correspondence to Bishnu P. Mukhopadhyay.

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Nandi, T.K., Bairagya, H.R., Mishra, D.K. et al. Structural and Putative Functional Role of Conserved Water Molecular Cluster in the X-ray Structures of Plant Thiol Proteases: A Molecular Dynamics Simulation Study. J Chem Crystallogr 42, 1105–1118 (2012). https://doi.org/10.1007/s10870-012-0364-z

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