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Computational study of the putative active form of protein Z (PZa): sequence design and structural modeling.

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.

SUBMITTER: Chandrasekaran V

PROVIDER: S-EPMC2492813 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Computational study of the putative active form of protein Z (PZa): sequence design and structural modeling.

Chandrasekaran Vasu V Lee Chang Jun CJ Duke Robert E RE Perera Lalith L Pedersen Lee G LG

Protein science : a publication of the Protein Society 20080520 8

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 propos ...[more]

PMID: 18493021

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