Sandbox Reserved 596
From Proteopedia
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'''Function''' | '''Function''' | ||
| - | The function of PZ was studied in 1991 by Hogg and Stenflo, who initially hypothesized PZ to amplify the coagulation cascade but found that bovine PZ has a higher affinity for thrombin than human PZ due to a 36 amino acid addition to the bovine PZ's C-terminus. Furthermore, they found that PZ virtually had no involvement in binding thrombin to phospholipids. It was not until 1998 that Han et al. described PZ present in the body as a complex with protein Z-dependent protease inhibitor (ZPI). The ZPI and PZ complex acts as an inhibitor of factor Xa attached to the | + | The function of PZ was studied in 1991 by Hogg and Stenflo, who initially hypothesized PZ to amplify the coagulation cascade but found that bovine PZ has a higher affinity for thrombin than human PZ due to a 36 amino acid addition to the bovine PZ's C-terminus. Furthermore, they found that PZ virtually had no involvement in binding thrombin to phospholipids. It was not until 1998 that Han et al. described PZ present in the body as a complex with protein Z-dependent protease inhibitor (ZPI). The ZPI and PZ complex acts as an inhibitor of factor Xa attached to the membrane surface (forming a calcium-dependent teritary complex). It is still unknown if the PZ and ZPI travel the body as a complex or if the complex forms at the phospholipid bilayer. While ZPI needs PZ, phospholipids, and calcium present to inhibit factor Xa, ZPI does not require other components to inhibit another coagulation factor XI. |
'''Clinical Relevance''' | '''Clinical Relevance''' | ||
'''References''' | '''References''' | ||
Revision as of 02:48, 7 April 2013
| This Sandbox is Reserved from Feb 1, 2013, through May 10, 2013 for use in the course "Biochemistry" taught by Irma Santoro at the Reinhardt University. This reservation includes Sandbox Reserved 591 through Sandbox Reserved 599. |
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Protein Z
Table of Contents
Background
Protein Z (PZ) is a vitamin k-dependent glycoprotein made in the liver and involved in the blood-clot-forming coagulation cascade. Bovine PZ was first identified by Prowse and Esnouf in 1977 and Human PZ was first isolated and studied by Broze Jr. and Miletich in 1984. The gene coding for PZ, called PROZ, was found in 1998 on chromosome 13 at location 13q34 and is composed of nine exons (one being an alternative exon).
Structure
PZ is a single-chain protein with a N-terminal domain rich in γ-carboxyglutamic acids, two epidermal growth factor-like domains and a C-terminal serine protease-like domain and has a molecular weight of 62 kDa. PZ genetically and structurally mimics other factors of the coagulation cascade but it is not a catalyticaly active enzyme. PZ is not like the other vitamin k-dependent coagulation factors because it does not have an active center, thus it lacks the serine needed for the active site of serine proteases, like the coagulation factors VII, IX, X, and protein C. PZ's 390 amino acid sequence is N-terminally analogous to the serine protease coagulation factors, whose similarly composed genes are found clustered together along with PROZ on chromosome 13.
Function
The function of PZ was studied in 1991 by Hogg and Stenflo, who initially hypothesized PZ to amplify the coagulation cascade but found that bovine PZ has a higher affinity for thrombin than human PZ due to a 36 amino acid addition to the bovine PZ's C-terminus. Furthermore, they found that PZ virtually had no involvement in binding thrombin to phospholipids. It was not until 1998 that Han et al. described PZ present in the body as a complex with protein Z-dependent protease inhibitor (ZPI). The ZPI and PZ complex acts as an inhibitor of factor Xa attached to the membrane surface (forming a calcium-dependent teritary complex). It is still unknown if the PZ and ZPI travel the body as a complex or if the complex forms at the phospholipid bilayer. While ZPI needs PZ, phospholipids, and calcium present to inhibit factor Xa, ZPI does not require other components to inhibit another coagulation factor XI.
Clinical Relevance
References
