Factor IX: Difference between revisions

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A [[pro-peptide]] functions as a recognition element for a vitamin K-dependent carboxylase (γ-glutamyl carboxylase) which modifies 12 glutamic acid residues to gamma-carboxyglutamyl (<scene name='Factor_IX/Ixstructure_residue/3'>Gla</scene>) residues<ref>PMID:12554099</ref>. These residues are required for the association with the anionic phospholipid surface through Ca2+-dependent binding.

The Gla Domain is followed by two epidermal growth factor domains (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> by a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>)<ref>PMID:11723140</ref>. <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> connects to the <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene> domain through a linker peptide that is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. To have a physiologically active factor IX, two cleavages must occur to remove a 35 amino acid region that precedes the catalytic site.

The Gla Domain is followed by two epidermal growth factor domains (<scene name='Factor_IX/Ixstructure_egf1/3'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/3'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> by a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>)<ref>PMID:11723140</ref>. <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> connects to the <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene> domain through a linker peptide that is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. To have a physiologically active factor IX, two cleavages must occur to remove a 35 amino acid region that precedes the catalytic site.

The first cleavage is at Arg145, generating an inactive FIXα. The second cleavage is at Arg180 results in a catalytically active molecule FIXaβ. This resulting heterodimer is held by a disulfide bridge at Cys132-Cys289. The <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene> contains a catalytic triad of <scene name='Factor_IX/Ixstructure_catalytictriad/2'>His221, Asp269, and Ser365</scene><ref>PMID:9374470</ref>. Upon cleave at Arg180, Val181 can form a salt bridge with Asp364, which is a characteristic of active <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. The active FIXa, can then interact with its cofactor, FVIIIa, to form a membrane-bound Xase complex, which activated FX to FXa.

Factor IX: Difference between revisions

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 A [[pro-peptide]] functions as a recognition element for a vitamin K-dependent carboxylase (γ-glutamyl carboxylase) which modifies 12 glutamic acid residues to gamma-carboxyglutamyl (<scene name='Factor_IX/Ixstructure_residue/3'>Gla</scene>) residues<ref>PMID:12554099</ref>. These residues are required for the association with the anionic phospholipid surface through Ca2+-dependent binding.
-The Gla Domain is followed by two epidermal growth factor domains (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> by a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>)<ref>PMID:11723140</ref>. <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> connects to the <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene> domain through a linker peptide that is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. To have a physiologically active factor IX, two cleavages must occur to remove a 35 amino acid region that precedes the catalytic site.
+The Gla Domain is followed by two epidermal growth factor domains (<scene name='Factor_IX/Ixstructure_egf1/3'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/3'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> by a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/2'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene>)<ref>PMID:11723140</ref>. <scene name='Factor_IX/Ixstructure_egf2/2'>EGF-2</scene> connects to the <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene> domain through a linker peptide that is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. To have a physiologically active factor IX, two cleavages must occur to remove a 35 amino acid region that precedes the catalytic site.
 The first cleavage is at Arg145, generating an inactive FIXα. The second cleavage is at Arg180 results in a catalytically active molecule FIXaβ. This resulting heterodimer is held by a disulfide bridge at Cys132-Cys289. The <scene name='Factor_IX/Ixstructure_chainc/2'>serine protease</scene>  contains a catalytic triad of <scene name='Factor_IX/Ixstructure_catalytictriad/2'>His221, Asp269, and Ser365</scene><ref>PMID:9374470</ref>. Upon cleave at Arg180, Val181 can form a salt bridge with Asp364, which is a characteristic of active <scene name='Factor_IX/Ixstructure_chainc/2'>serine proteases</scene>. The active FIXa, can then interact with its cofactor, FVIIIa, to form a membrane-bound Xase complex, which activated FX to FXa.