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Computational study of the putative active form of protein Z (PZa): Sequence design and structural modeling
Author(s) -
Chandrasekaran Vasu,
Lee Chang Jun,
Duke Robert E.,
Perera Lalith,
Pedersen Lee G.
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.034801.108
Subject(s) - serine protease , in silico , homology modeling , serine , docking (animal) , peptide sequence , protease , biochemistry , chemistry , protein superfamily , active site , protein structure , computational biology , molecular model , biology , enzyme , gene , medicine , nursing
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.