Lauren Ferris/Sandbox 1
From Proteopedia
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<Structure load='1aut' size='400' color='white' frame='true' align='left' caption='pdb: 1AUT' /> | <Structure load='1aut' size='400' color='white' frame='true' align='left' caption='pdb: 1AUT' /> | ||
| - | + | ==Introduction== | |
The vitamin K dependent zymogen Protein C is an integral component of the blood coagulation system. The blood coagulation system is composed of two pathways that converge to form the prothrombinase complex (FVa-FXa). Thrombin is generated from this complex and catalyzes the formation of the clot by activating Fibrinogen and FXIII. Thrombin will also bind to thrombomodulin and the complex removes 12 peptides(Arg169-Leu170) from the protein, converting the protein to the active form: Activated Protein C.<ref name="thrombo">PMID: 3029867</ref><ref name="thromboII">PMID: 8236111 </ref><ref name="thromboIII">PMID: 1912552 </ref> Activated Protein C will function as a down-regulator of procoagulant stimuli through the degradation of zymogens and their active counterparts: FV/FVa and FVIII/FVIIIa. <ref name="difI">PMID: 6687387 </ref><ref name="difII">PMID: 1939075</ref> This ability enables Protein C to modulate the coagulant response, preventing unchecked clotting. | The vitamin K dependent zymogen Protein C is an integral component of the blood coagulation system. The blood coagulation system is composed of two pathways that converge to form the prothrombinase complex (FVa-FXa). Thrombin is generated from this complex and catalyzes the formation of the clot by activating Fibrinogen and FXIII. Thrombin will also bind to thrombomodulin and the complex removes 12 peptides(Arg169-Leu170) from the protein, converting the protein to the active form: Activated Protein C.<ref name="thrombo">PMID: 3029867</ref><ref name="thromboII">PMID: 8236111 </ref><ref name="thromboIII">PMID: 1912552 </ref> Activated Protein C will function as a down-regulator of procoagulant stimuli through the degradation of zymogens and their active counterparts: FV/FVa and FVIII/FVIIIa. <ref name="difI">PMID: 6687387 </ref><ref name="difII">PMID: 1939075</ref> This ability enables Protein C to modulate the coagulant response, preventing unchecked clotting. | ||
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| - | <Structure load='1aut' size='400' color=blue='true' align='right' caption='pdb: 1AUT' /'> | + | <Structure load='1aut' size='400' color=blue='true' align='right' caption='pdb: 1AUT' scene='Lauren_Ferris/Sandbox_1/All/1'/'> |
| - | + | ==Structure== | |
Activated protein C is a spheroid shaped molecule with both alpha helices and beta sheets. The protein contains similar domains to other vitamin K dependent coagulation proteins with a heavy and light chain connected by a di-sulfide bond. The light chain contains a Gla domain and 2 epidermal growth factor domains, while the heavy chain contains an activated peptide domain and a serine protease domain. | Activated protein C is a spheroid shaped molecule with both alpha helices and beta sheets. The protein contains similar domains to other vitamin K dependent coagulation proteins with a heavy and light chain connected by a di-sulfide bond. The light chain contains a Gla domain and 2 epidermal growth factor domains, while the heavy chain contains an activated peptide domain and a serine protease domain. | ||
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| - | + | ==Mechanism== | |
Activated Protein C is a serine protease and utilizes residues Aspartic Acid 257, Histidine 211, and Serine 360 to cleave factors FV and FVIII as well as their activated forms. Protein C has been shown to be a highly functional enzyme functioning in the presence of membrane bound and unbound substrate, while being resistant to a variety of inhibitors. Activate Protein C has been shown to cleave FV only in the presence of a phospholipid bilayer at Arg 306 first, followed by Arg 506, and then Arg 679 and Lys 994. Under these conditions cleavage at Arg 306 is insufficient for inactivation. Activated Protein C can also degrade FVa....... | Activated Protein C is a serine protease and utilizes residues Aspartic Acid 257, Histidine 211, and Serine 360 to cleave factors FV and FVIII as well as their activated forms. Protein C has been shown to be a highly functional enzyme functioning in the presence of membrane bound and unbound substrate, while being resistant to a variety of inhibitors. Activate Protein C has been shown to cleave FV only in the presence of a phospholipid bilayer at Arg 306 first, followed by Arg 506, and then Arg 679 and Lys 994. Under these conditions cleavage at Arg 306 is insufficient for inactivation. Activated Protein C can also degrade FVa....... | ||
Protein C functions best in the presence of a phospholipid bilayer and with its cofactor Protein S. | Protein C functions best in the presence of a phospholipid bilayer and with its cofactor Protein S. | ||
Revision as of 01:53, 15 May 2012
Activated Protein C
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Introduction
The vitamin K dependent zymogen Protein C is an integral component of the blood coagulation system. The blood coagulation system is composed of two pathways that converge to form the prothrombinase complex (FVa-FXa). Thrombin is generated from this complex and catalyzes the formation of the clot by activating Fibrinogen and FXIII. Thrombin will also bind to thrombomodulin and the complex removes 12 peptides(Arg169-Leu170) from the protein, converting the protein to the active form: Activated Protein C.[1][2][3] Activated Protein C will function as a down-regulator of procoagulant stimuli through the degradation of zymogens and their active counterparts: FV/FVa and FVIII/FVIIIa. [4][5] This ability enables Protein C to modulate the coagulant response, preventing unchecked clotting.
Protein C has also been recognized for its role in anti-inflammatory and cytoprotective signaling responses in endothelial cells. Protein C will bind to an endothelial protein c receptor (EPCR) and then activate protease-activated receptor (PAR-1).[6]
Protein C is synthesized in the liver and circulates the blood at a concentration of 4 ug/mL. The liver conformation is a single polypeptide sequence with an additional 42 amino acids attached at the N-terminus. This structure is known as the pre-pro sequence. Subsequent removal of these peptides as well as Lys156-Arg157 will result in the 62 kD protein that is often observed.[7]
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