Crystallographic structure protein Z.
|Locus||Chr. 13 q34|
Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.
Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.
The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.
In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.
Structural analysis of protein Z will allow better understanding of its function. From a Ramachandran plot, the secondary structure of Protein Z was determined. The Ramachandran plot utilizes mathematical equations to determine the possible angles of the amino acids within the primary sequence of Protein Z. The possible angles results in a plot of possible secondary structures. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.
- PDB 1LP1: Högbom M, Eklund M, Nygren PA, Nordlund P (March 2003). "Structural basis for recognition by an in vitro evolved affibody". Proc. Natl. Acad. Sci. U.S.A. 100 (6): 3191–6. doi:10.1073/pnas.0436100100. PMC 404300. PMID 12604795.
- Ichinose A, Takeya H, Espling E, Iwanaga S, Kisiel W, Davie EW (November 1990). "Amino acid sequence of human protein Z, a vitamin K-dependent plasma glycoprotein". Biochem. Biophys. Res. Commun. 172 (3): 1139–44. doi:10.1016/0006-291X(90)91566-B. PMID 2244898.
- Sejima H, Hayashi T, Deyashiki Y, Nishioka J, Suzuki K (September 1990). "Primary structure of vitamin K-dependent human protein Z". Biochem. Biophys. Res. Commun. 171 (2): 661–8. doi:10.1016/0006-291X(90)91197-Z. PMID 2403355.
- Prowse CV, Esnouf MP (1977). "The isolation of a new warfarin-sensitive protein from bovine plasma". Biochem. Soc. Trans. 5 (1): 255–6. PMID 892175.
- Broze GJ, Miletich JP (April 1984). "Human Protein Z". J. Clin. Invest. 73 (4): 933–8. doi:10.1172/JCI111317. PMC 425104. PMID 6707212.