Sandbox Reserved 596: Difference between revisions
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[[Protein Z]] | [[Protein Z]] | ||
[[Structure]] | [[Structure]] | ||
[[Function]] | [[Function]] | ||
[[Protein Z-Dependent Protease Inhibitor]] | [[Protein Z-Dependent Protease Inhibitor]] | ||
[[Structure]] | [[Structure]] | ||
[[Function]] | [[Function]] | ||
[[PZ-ZPI Complex FXa Inhibition]] | [[PZ-ZPI Complex FXa Inhibition]] | ||
[[References]] | [[References]] | ||
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'''PZ''' | '''PZ''' | ||
Bovine PZ was first identified by Prowse and Esnouf in 1977 and human PZ, consisting of 360 amino acid residues and having a molecular weight of 62kDa, was first isolated and studied by Broze Jr. and Miletich in 1984. The gene coding for human PZ, PROZ, was found in 1998 on chromosome 13 at location 13q34 and is composed of a 389 bp promoter and nine exons (one being an alternative exon). [1,4] PZ is a single-chain glycoprotein with a 13 γ-carboxyglutamic (residues 7, 8, 11, 15, 17, 20, 21, 26, 27, 30, 33, 35 and 40) acid residues (Gla) N-terminal domain (residues 1-46), two epithelial growth factor (EGF)-like domains (EGF1 residues 47-830, EGF2 residues 85-126), and a C-terminal serine protease (SP)- like domain (residues 135-360) (Figure 1). | Bovine PZ was first identified by Prowse and Esnouf in 1977 and human PZ, consisting of 360 amino acid residues and having a molecular weight of 62kDa, was first isolated and studied by Broze Jr. and Miletich in 1984. The gene coding for human PZ, PROZ, was found in 1998 on chromosome 13 at location 13q34 and is composed of a 389 bp promoter and nine exons (one being an alternative exon). [1,4] PZ is a single-chain glycoprotein with a 13 γ-carboxyglutamic (residues 7, 8, 11, 15, 17, 20, 21, 26, 27, 30, 33, 35 and 40) acid residues (Gla) N-terminal domain (residues 1-46), two epithelial growth factor (EGF)-like domains (EGF1 residues 47-830, EGF2 residues 85-126), and a C-terminal serine protease (SP)- like domain (residues 135-360) (Figure 1). | ||
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'''ZPI''' | '''ZPI''' | ||
<Structure load='3F1S' size='500' frame='true' align='right' caption='Protein Z (green) and Protein Z Dependent Inhibitor (blue) Complex' scene='Insert optional scene name here' /> | |||
ZPI, a single-chain glycoprotein made in the liver with 423 residues and a molecular weight of 72 kDa, was first isolated in human plasma in 1998. ZPI is coded for by the gene SERPINA10 at locus 14q32.13 and is 25-35% homologous in its amino acid sequence to the serpin family of protease inhibitors.[7] Structurally ZPI has a characteristic serpin fold with three main β-sheets and exposed reactive center loop (Figure 3). The ZPI binding site for PZ is centered around its helix G (hG) and helix A (hA) while PZ’s bind site for ZPI is centered around its SP anion-binding site near the C-terminal. ZPI also has an atypical hydrogen bond configuration at the shutter region with the Asn186 of usual serpins being replaced by an aspartate (D213) in ZPI. This causes a different pattern of hydrogen bonds and the resulting placement of the D213 into a hydrophobic area underneath ZPI’s β-sheet A. D213 can therefore only form 1 hydrogen bond, compared to other serpins like antitrypsin and PAI-1 that form 4 and 3 hydrogen bonds respectively. [4] | ZPI, a single-chain glycoprotein made in the liver with 423 residues and a molecular weight of 72 kDa, was first isolated in human plasma in 1998. ZPI is coded for by the gene SERPINA10 at locus 14q32.13 and is 25-35% homologous in its amino acid sequence to the serpin family of protease inhibitors.[7] Structurally ZPI has a characteristic serpin fold with three main β-sheets and exposed reactive center loop (Figure 3). The ZPI binding site for PZ is centered around its helix G (hG) and helix A (hA) while PZ’s bind site for ZPI is centered around its SP anion-binding site near the C-terminal. ZPI also has an atypical hydrogen bond configuration at the shutter region with the Asn186 of usual serpins being replaced by an aspartate (D213) in ZPI. This causes a different pattern of hydrogen bonds and the resulting placement of the D213 into a hydrophobic area underneath ZPI’s β-sheet A. D213 can therefore only form 1 hydrogen bond, compared to other serpins like antitrypsin and PAI-1 that form 4 and 3 hydrogen bonds respectively. [4] | ||
