Factor IX: Difference between revisions
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<span style="color:Brown">'''''γ''-Carboxylation Reaction'''</span> is catalyzed by the γ-glutamyl carboxylase in the ER and requires a reduced form of vitamin K, oxygen, and carbon dioxide. The reaction is initiated by the removal of a hydrogen atom at the γ position of glutamate. This reaction creates a carbon ion that reacts with carbon dioxide thus forming γ-carboxy glutamic acid. As the protein is carboxylated using carbon dioxide the reduced vitamin K (hydroquinone) is oxidized to epoxide. | <span style="color:Brown">'''''γ''-Carboxylation Reaction'''</span> is catalyzed by the γ-glutamyl carboxylase in the ER and requires a reduced form of vitamin K, oxygen, and carbon dioxide<ref>PMID:10068650</ref>. The reaction is initiated by the removal of a hydrogen atom at the γ position of glutamate. This reaction creates a carbon ion that reacts with carbon dioxide thus forming γ-carboxy glutamic acid. As the protein is carboxylated using carbon dioxide the reduced vitamin K (hydroquinone) is oxidized to epoxide. | ||
In order for this reaction to continue vitamin K must be regenerated, which is carried out by nicotinamide phosphate, thus allowing the continuation of the cycle. Protein carboxylation, provides a region which allows the protein to associate with the membrane anionic phospholipid surface, thus allowing close proximity to other components of coagulation. Without vitamin K, coagulation precursor proteins would circulate through the plasma, but would have minimal function. | In order for this reaction to continue vitamin K must be regenerated, which is carried out by nicotinamide phosphate, thus allowing the continuation of the cycle. Protein carboxylation, provides a region which allows the protein to associate with the membrane anionic phospholipid surface, thus allowing close proximity to other components of coagulation. Without vitamin K, coagulation precursor proteins would circulate through the plasma, but would have minimal function. | ||
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== γ-Carboxyglutamic Acid (Gla) Domain == | == γ-Carboxyglutamic Acid (Gla) Domain == | ||
{{STRUCTURE_1j35| PDB=1j35 | SCENE= }} | {{STRUCTURE_1j35| PDB=1j35 | SCENE= }} | ||
The Gla domain is situated at the N-terminus of coagulation factor IX, and is evolutionary conserved in other vitamin K dependent proteins such as factor VII, X, and prothrombin. A <scene name='Factor_IX/Gladomain_glamgca/2'>Gla domain</scene> is made up of 10-13 of γ-carboxyglutamic acid residues and requires both <scene name='Factor_IX/Gladomain_1/6'>Ca2+ and Mg2+ </scene> ions for membrane association and stabilization of its active three dimensional conformation | The Gla domain is situated at the N-terminus of coagulation factor IX, and is evolutionary conserved in other vitamin K dependent proteins such as factor VII, X, and prothrombin. A <scene name='Factor_IX/Gladomain_glamgca/2'>Gla domain</scene> is made up of 10-13 of γ-carboxyglutamic acid residues and requires both <scene name='Factor_IX/Gladomain_1/6'>Ca2+ and Mg2+ </scene> ions for membrane association and stabilization of its active three dimensional conformation <ref>PMID:3511981</ref>. | ||
In the presence of [[calcium ions the Gla domain]] (Calcium ions 5 and 6 and Gla residues 17 and 21) interacts with serine head group of phosphatidylserine located on the phospholipid membrane (2). In the absence of metal ions the Gla domain is highly disordered and unstructured which indicated that the metal ions, stabilize the structure (4-6). Three Mg2+ ions, (Mg-1, Mg-7, and Mg-8) are located on the surface of FIX and correspond to FX, three Ca2+ ions (Ca-1, Ca-7, and Ca-8). Each Mg2+ ion has a <scene name='Factor_IX/Gladomain_1/7'>bipyramidal coordination</scene> with a water molecule (Mg–O in FIX is 2.12 Å, whereas the Ca–O distances in FX is 2.41 Å) and a pair of Gla residues. | In the presence of [[calcium ions the Gla domain]] (Calcium ions 5 and 6 and Gla residues 17 and 21) interacts with serine head group of phosphatidylserine located on the phospholipid membrane (2). In the absence of metal ions the Gla domain is highly disordered and unstructured which indicated that the metal ions, stabilize the structure (4-6). Three Mg2+ ions, (Mg-1, Mg-7, and Mg-8) are located on the surface of FIX and correspond to FX, three Ca2+ ions (Ca-1, Ca-7, and Ca-8). Each Mg2+ ion has a <scene name='Factor_IX/Gladomain_1/7'>bipyramidal coordination</scene> with a water molecule (Mg–O in FIX is 2.12 Å, whereas the Ca–O distances in FX is 2.41 Å) and a pair of Gla residues. | ||
