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Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid–base coupled mechanism in plant thiol protease

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Abstract

Cysteine protease is ubiquitous in nature. Excess activity of this enzyme causes intercellular proteolysis, muscle tissue degradation, etc. The role of water-mediated interactions in the stabilization of catalytically significant Asp158 and His159 was investigated by performing molecular dynamics simulation studies of 16 three-dimensional structures of plant thiol proteases. In the simulated structures, the hydrophilic W1, W2 and WD1 centers form hydrogen bonds with the OD1 atom of Asp158 and the ND1 atom of His159. In the solvated structures, another water molecule, WE, forms a hydrogen bond with the NE2 atom of His159. In the absence of the water molecule WE, Trp177 (NE1) and Gln19 (NE2) directly interact with the NE2 atom of His159. All these hydrophilic centers (the locations of W1, W2, WD1, and WE) are conserved, and they play a critical role in the stabilization of His–Asp complexes. In the water dynamics of solvated structures, the water molecules W1 and W2 form a water...water hydrogen-bonded network with a few other water molecules. A few dynamical conformations or transition states involving direct (His159 ND1...Asp158 OD1) and water-mediated (His159 ND1...W2...Asp158 OD1) hydrogen-bonded complexes are envisaged from these studies.

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Acknowledgments

We thank and acknowledge the National Institute of Technology Durgapur for providing a research facility in the Department of Chemistry. We also thank and acknowledge Dr. K Sekar, Indian Institute of Science, Bangalore, India, for critically reading this manuscript.

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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, Bishnu P. Mukhopadhyay, Payel Mallik & Dipankar Sukul

  2. Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA

    Asim K. Bera

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  1. Tapas K. Nandi
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  2. Hridoy R. Bairagya
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  3. Bishnu P. Mukhopadhyay
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Correspondence to Bishnu P. Mukhopadhyay.

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Nandi, T.K., Bairagya, H.R., Mukhopadhyay, B.P. et al. Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid–base coupled mechanism in plant thiol protease. J Mol Model 18, 2633–2644 (2012). https://doi.org/10.1007/s00894-011-1277-z

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  • DOI: https://doi.org/10.1007/s00894-011-1277-z

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