Factor IX: Difference between revisions
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== γ-Carboxyglutamic Acid (Gla) Domain == | == γ-Carboxyglutamic Acid (Gla) Domain == | ||
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The Gla domain perhaps also interacts with factor VIIIa via Mg2+-binding sites. Membrane bound FIXa forms an arched structure which is seen in the spatial relationship among the Gla, epidermal growth factor, and serine protease domains. This arched allows for the formation of a concave surface on the right side of FIXa and acts as a binding site for factor VIIIa. The Mg-8 ion points toward this concave surface making it ideal in the interaction between FIXa and GVIIIa. Similarly, [[Mg-8 may contribute to the binding to factors VIIa and X]]. | The Gla domain perhaps also interacts with factor VIIIa via Mg2+-binding sites. Membrane bound FIXa forms an arched structure which is seen in the spatial relationship among the Gla, epidermal growth factor, and serine protease domains. This arched allows for the formation of a concave surface on the right side of FIXa and acts as a binding site for factor VIIIa. The Mg-8 ion points toward this concave surface making it ideal in the interaction between FIXa and GVIIIa. Similarly, [[Mg-8 may contribute to the binding to factors VIIa and X]]. | ||
Bovine <scene name='Factor_IX/Ixstructure/2'>Factor IX -(1-46)</scene> bound to a snake venom protein (Factor IX-bp), is crystallized in the presence of calcium and magnesium ions and in the presence of calcium alone. | Bovine <scene name='Factor_IX/Ixstructure/2'target='>Factor IX -(1-46)</scene> bound to a snake venom protein (Factor IX-bp), is crystallized in the presence of calcium and magnesium ions and in the presence of calcium alone. | ||
This structure emphasizes the possible role of magnesium in Gla domain binding to membrane surfaces. However upon examination of the calcium bound Factor IX-(1-46) complex revealed that the calcium coordination within this FIX Gla domain structure differes from other vitamin K-dependent proteins (prothrombin (7), Factor VII (10), and Factor X (11)). This deviation may be explained by the interaction of the snake venom FIX-bp interaction (this reference). | This structure emphasizes the possible role of magnesium in Gla domain binding to membrane surfaces. However upon examination of the calcium bound Factor IX-(1-46) complex revealed that the calcium coordination within this FIX Gla domain structure differes from other vitamin K-dependent proteins (prothrombin (7), Factor VII (10), and Factor X (11)). This deviation may be explained by the interaction of the snake venom FIX-bp interaction (this reference). | ||
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The serine protease domain of FIX is required for blood coagulation. FIX circulates in plasma as a single-chain zymogen at a concentration of 2.5-5 mg/ml and a half life is approximately 24 hours. The zymogen is activated by either FVII–tissue-factor complex or Factor XIa (FXIa). During activation the peptide bonds betweennArg145–Ala146 and Arg180–Val181 are cleaved releasing an 11 kDa activation peptide from the Factor IX. This cleavage allows the exposure of the serine protease site on the heavy chain which can then activate Factor X in the presence of Factor VIII, Ca and phospholipid surface. This enzyme belongs to the family of trypsin-like serine proteases.The mechanism of these serine proteases involves the catalytic triad, which is found in the enzymes active site and is composed of three amino acids. | The serine protease domain of FIX is required for blood coagulation. FIX circulates in plasma as a single-chain zymogen at a concentration of 2.5-5 mg/ml and a half life is approximately 24 hours. The zymogen is activated by either FVII–tissue-factor complex or Factor XIa (FXIa). During activation the peptide bonds betweennArg145–Ala146 and Arg180–Val181 are cleaved releasing an 11 kDa activation peptide from the Factor IX. This cleavage allows the exposure of the serine protease site on the heavy chain which can then activate Factor X in the presence of Factor VIII, Ca and phospholipid surface. This enzyme belongs to the family of trypsin-like serine proteases.The mechanism of these serine proteases involves the catalytic triad, which is found in the enzymes active site and is composed of three amino acids. | ||
