Factor IX: Difference between revisions
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<applet load='1lbg' size='450' frame='true' align='right' scene='Factor_IX/Ixstructure/2' /> | <applet load='1lbg' size='450' frame='true' align='right' scene='Factor_IX/Ixstructure/2' /> | ||
'''Factor IX''' (plasma thromboplastin component, Christmas factor, or hemophilia B factor) is a 57-kDa vitamin K-dependent procoagulant glycoprotein. It is synthesized by the liver hepatocyte as a [[pre-prozymogen]] that requires extensive posttranslational modification. The [[pre-prozymogen]] contains a pre-peptide (hydrophobic signal peptide) at its amino terminal that transports the growing polypeptide into the lumen of the Endoplasmic Reticulum. Once inside the ER, this signal peptide is cleaved by a signal peptidase. 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/1'>Residue</scene>) residues. 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 ( | |||
'''Factor IX''' (plasma thromboplastin component, Christmas factor, or hemophilia B factor) is a 57-kDa vitamin K-dependent procoagulant glycoprotein. It is synthesized by the liver hepatocyte as a [[pre-prozymogen]] that requires extensive posttranslational modification. The [[pre-prozymogen]] contains a pre-peptide (hydrophobic signal peptide) at its amino terminal that transports the growing polypeptide into the lumen of the Endoplasmic Reticulum. Once inside the ER, this signal peptide is cleaved by a signal peptidase. 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_egf1/1'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/1'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene> and a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/1'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene>). <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene> connects to the scene name='Factor_IX/Ixstructure_chainc/1'>serine protease</scene> domain through a linker peptide and is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/1'>serine proteases</scene>. To have a physiologically active factor IX, two cleaves must occur to remove a 35 amino acid region that precedes the catalytic region. The first cleave 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/1'>serine protease</scene> contains a catalytic triad of <scene name='Factor_IX/Ixstructure_catalytictriad/1'>His221, Asp269, and Ser365</scene>. Upon cleave at Arg180, Val181 can form a salt bridge with Asp364, which is a characteristic of active <scene name='Factor_IX/Ixstructure_chainc/1'>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. | <scene name='Factor_IX/Ixstructure_egf1/1'>EGF-1</scene> and <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene>). The N-terminus of <scene name='Factor_IX/Ixstructure_egf1/1'>EGF-1</scene> contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene> and a salt bridge through Lys122 (<scene name='Factor_IX/Ixstructure_egf1/1'>EGF-1</scene> residue) and Gln74 (<scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene>). <scene name='Factor_IX/Ixstructure_egf2/1'>EGF-2</scene> connects to the scene name='Factor_IX/Ixstructure_chainc/1'>serine protease</scene> domain through a linker peptide and is required for a proper orientation and folding of <scene name='Factor_IX/Ixstructure_chainc/1'>serine proteases</scene>. To have a physiologically active factor IX, two cleaves must occur to remove a 35 amino acid region that precedes the catalytic region. The first cleave 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/1'>serine protease</scene> contains a catalytic triad of <scene name='Factor_IX/Ixstructure_catalytictriad/1'>His221, Asp269, and Ser365</scene>. Upon cleave at Arg180, Val181 can form a salt bridge with Asp364, which is a characteristic of active <scene name='Factor_IX/Ixstructure_chainc/1'>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. | ||
Revision as of 23:35, 19 April 2009
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Factor IX (plasma thromboplastin component, Christmas factor, or hemophilia B factor) is a 57-kDa vitamin K-dependent procoagulant glycoprotein. It is synthesized by the liver hepatocyte as a pre-prozymogen that requires extensive posttranslational modification. The pre-prozymogen contains a pre-peptide (hydrophobic signal peptide) at its amino terminal that transports the growing polypeptide into the lumen of the Endoplasmic Reticulum. Once inside the ER, this signal peptide is cleaved by a signal peptidase. 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 (
) residues. 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 (
and ). The N-terminus of contains a Ca2+ binding site, while the C-terminus connects to a hydrophobic pocket of and a salt bridge through Lys122 ( residue) and Gln74 (). connects to the scene name='Factor_IX/Ixstructure_chainc/1'>serine protease</scene> domain through a linker peptide and is required for a proper orientation and folding of . To have a physiologically active factor IX, two cleaves must occur to remove a 35 amino acid region that precedes the catalytic region. The first cleave 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 contains a catalytic triad of . Upon cleave at Arg180, Val181 can form a salt bridge with Asp364, which is a characteristic of active . The active FIXa, can then interact with its cofactor, FVIIIa, to form a membrane-bound Xase complex, which activated FX to FXa.
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