User:Jessicabiochem/Protein Z

Protein Z (PZ or PROZ) is a protein which in humans is encoded by the PROZ gene.

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.

Physiology

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.

Genetics

It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).

It has four domains: a gla-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.

History

Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977, and Broze & Miletich determined it in human plasma in 1984. Protein Z was found in cattle first before it was found humans, the protein that was found in humans was given the same name as what was found in cattle for a few reasons. When looking at these isolated proteins it was found that they both have similar molecular weight, a similar composition of amino acids, and a similar NH2- Terminal sequences.[1] These similarities in molecular composition of the protein found in cattle and humans were great enough that it can be concluded they were the same protein. When Protein Z was first discovered, it was theorized to be a form of Factor X instead of its own individual protein. More studies had to be done to isolate this protein to find out if it was a form of factor X or not. To do this research it took the process of separating the protein from plasma using immunoelectrophoresis. The first step of the process involved removing the vitamin K dependents from the plasma. This was possible by adsorption to barium citrate. Then the next step that was taken was chromatography to further separate these proteins from each other. For Protein Z an agarose-based ion exchange was used to have the best separation. This process showed that there was no factor X in the isolated protein. This meant that Protein Z was a separate protein from factor X.[2] This study showed that Protein Z while theorized to be a form of factor X, it wasn't. Since there was not factor X in the newly isolated protein it could be concluded it was a separate protein.

Structure

Structural analysis of protein Z will allow better understanding of its function. 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.

Protein Z is made up with two different chains. Both of these chains have some side chains and ligands attached to them. The protein has sections that are charged. Protein Z appears to have two domains that are identical to each other. The amino acids are the same of these chains are the exact same as is the secondary structures, side chains and the ligands that branch off.