Computational study of the putative active form of protein Z (PZa): sequence design and structural modeling |
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Authors: | Chandrasekaran Vasu Lee Chang Jun Duke Robert E Perera Lalith Pedersen Lee G |
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Affiliation: | Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. |
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Abstract: | Although protein Z (PZ) has a domain arrangement similar to the essential coagulation proteins FVII, FIX, FX, and protein C, its serine protease (SP)-like domain is incomplete and does not exhibit proteolytic activity. We have generated a trial sequence of putative activated protein Z (PZa) by identifying amino acid mutations in the SP-like domain that might reasonably resurrect the serine protease catalytic activity of PZ. The structure of the activated form was then modeled based on the proposed sequence using homology modeling and solvent-equilibrated molecular dynamics simulations. In silico docking of inhibitors of FVIIa and FXa to the putative active site of equilibrated PZa, along with structural comparison with its homologous proteins, suggest that the designed PZa can possibly act as a serine protease. |
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Keywords: | protein Z (PZ) sequence design active form of protein Z (PZa) homology modeling molecular dynamics simulation molecular docking |
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