User:Burcu Baykal/Sandbox1 - Revision history

Burcu Baykal at 03:21, 10 December 2008

Burcu Baykal — Wed, 10 Dec 2008 03:21:47 GMT

←Older revision		Revision as of 03:21, 10 December 2008
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	==References==		==References==
	1.Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J.Mol.Biol. 322: 591-603 2002		1.Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J.Mol.Biol. 322: 591-603 2002
		+
	2.Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 404: 465-470 2000		2.Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 404: 465-470 2000

Burcu Baykal at 03:20, 10 December 2008

Burcu Baykal — Wed, 10 Dec 2008 03:20:59 GMT

←Older revision		Revision as of 03:20, 10 December 2008
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-	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.	+	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.<ref=1>


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	[[Image:Deve.png\|left\|250px]]		[[Image:Deve.png\|left\|250px]]

-	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.The figure shows the contact region of E-76 peptide inhibitor on FVIIa surface.	+	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.The figure shows the contact region of E-76 peptide inhibitor on FVIIa surface.<ref=2>


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	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>		<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>
		+
		+	==References==
		+	1.Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions. J.Mol.Biol. 322: 591-603 2002
		+	2.Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 404: 465-470 2000

Burcu Baykal at 10:15, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:15:22 GMT

←Older revision		Revision as of 10:15, 9 December 2008
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	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.		It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.
-
-
-	[[Image:FVIIa uninhibited.png\|left\|250px]]
-
-

Burcu Baykal at 10:14, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:14:36 GMT

←Older revision		Revision as of 10:14, 9 December 2008
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	'''Inhibition of FVIIa-TF Complex'''		'''Inhibition of FVIIa-TF Complex'''
		+
		+	[[Image:Deve.png\|left\|250px]]

	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.The figure shows the contact region of E-76 peptide inhibitor on FVIIa surface.		Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.The figure shows the contact region of E-76 peptide inhibitor on FVIIa surface.
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-	~~[[Image:Deve.png\|left\|250px]]~~	+

Burcu Baykal at 10:13, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:13:34 GMT

←Older revision		Revision as of 10:13, 9 December 2008
Line 5:		Line 5:

	Extrinsic cascade is activated upon a vascular damage by factor VII/VIIa and its membrane bound co-factor tissue factor(TF).The balance between hemostasis and thrombosis is very crucial that excessive cloth formation can be prevented by anticoagulants. Heparin-[[ATII]] is the most known anticoagulant that targets FXa and thrombi in the cascade. since the coagulation process starts with FVIIa-TF complex; it can be a very good therapeutic anticoagulant.		Extrinsic cascade is activated upon a vascular damage by factor VII/VIIa and its membrane bound co-factor tissue factor(TF).The balance between hemostasis and thrombosis is very crucial that excessive cloth formation can be prevented by anticoagulants. Heparin-[[ATII]] is the most known anticoagulant that targets FXa and thrombi in the cascade. since the coagulation process starts with FVIIa-TF complex; it can be a very good therapeutic anticoagulant.
		+
		+	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/1'>TextToBeDisplayed</scene>
		+	<applet load='1klj' size='300' frame='true' align='right' caption='Insert caption here' />

	'''Factor VIIa'''		'''Factor VIIa'''
		+
		+

	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.		It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.
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-	~~<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/1'>TextToBeDisplayed</scene>~~	+
-	~~<applet load='1klj' size='300' frame='true' align='right' caption='Insert caption here' />~~	+


	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>		<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>

Burcu Baykal at 10:12, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:12:09 GMT

←Older revision		Revision as of 10:12, 9 December 2008
Line 9:		Line 9:

	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.		It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.
		+

	[[Image:FVIIa uninhibited.png\|left\|250px]]		[[Image:FVIIa uninhibited.png\|left\|250px]]
		+
		+
		+
		+

	'''Inhibition of FVIIa-TF Complex'''		'''Inhibition of FVIIa-TF Complex'''

-	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.	+	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.The figure shows the contact region of E-76 peptide inhibitor on FVIIa surface.

		+

-	~~The figure shows the contact~~ [[Image:Deve.png\|left\|250px]]	+	[[Image:Deve.png\|left\|250px]]
-	~~region of E-76 peptide inhibitor~~	+
-	~~on FVIIa surface.~~	+

Burcu Baykal at 10:10, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:10:54 GMT

←Older revision		Revision as of 10:10, 9 December 2008
Line 12:		Line 12:
	[[Image:FVIIa uninhibited.png\|left\|250px]]		[[Image:FVIIa uninhibited.png\|left\|250px]]

		+	'''Inhibition of FVIIa-TF Complex'''

		+	Human TF-FVIIa complex is inhibited by TFPI.It interacts with the catalytic triad at the active site either by reversible or irreversible. A new class of peptide inhibitors of FVIIa discvered using phage display that inhibites at the exosite on the TF-FVIIa complex.Polyvalent phage libraries searched and a `fully matured' consensus sequence; peptide E-76 (Ac-ALCDDPRVDRWYCQFVEG-NH2) was chosen for further characterization.The same dissociation constant found with FVIIa or TF±FVIIa by Surface plasmon resonance studies.No evidence for binding was detected for TF or thrombin, FXa,FIXa, FXIa, FXIIa, plasma kallikrein, activated protein C, tissue plasminogen activator (t-PA) and plasmin.Also,Binding to FVIIa was dependent on the presence of calcium.


-		+	The figure shows the contact [[Image:Deve.png\|left\|250px]]
-		+	region of E-76 peptide inhibitor
-		+	on FVIIa surface.
-		+
-		+
-		+
-		+
-		+
-		+
-		+
-		+
-		+


	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/1'>TextToBeDisplayed</scene>		<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/1'>TextToBeDisplayed</scene>
	<applet load='1klj' size='300' frame='true' align='right' caption='Insert caption here' />		<applet load='1klj' size='300' frame='true' align='right' caption='Insert caption here' />
-	~~[[Image:oxy.jpg]]~~	+

	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>		<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>
-	[[Image:Klj a.png\|left\|400px]]

Burcu Baykal at 10:00, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 10:00:35 GMT

←Older revision		Revision as of 10:00, 9 December 2008
Line 3:		Line 3:
	Secondary hemostasis is a complex system resulting fibrin formation as an output of the interaction between coagulation factors. Coagulation factors are serine proteases that forms coagulation cascade. It can be initiated via two different pathways: intrinsic and extrinsic.		Secondary hemostasis is a complex system resulting fibrin formation as an output of the interaction between coagulation factors. Coagulation factors are serine proteases that forms coagulation cascade. It can be initiated via two different pathways: intrinsic and extrinsic.
	[[Image:Cascade.jpg.png\|left\|100px]]		[[Image:Cascade.jpg.png\|left\|100px]]
		+
		+	Extrinsic cascade is activated upon a vascular damage by factor VII/VIIa and its membrane bound co-factor tissue factor(TF).The balance between hemostasis and thrombosis is very crucial that excessive cloth formation can be prevented by anticoagulants. Heparin-[[ATII]] is the most known anticoagulant that targets FXa and thrombi in the cascade. since the coagulation process starts with FVIIa-TF complex; it can be a very good therapeutic anticoagulant.
		+
		+	'''Factor VIIa'''
		+
		+	It is composed of 254-residue serine protease domain in the heavy chain and two EGF-like domains with a Gla domain in the light chain. Catalytic domain includes two six-stranded antiparallel β-barrels with the active-site cleft between them.N terminal Ile16 stabilizes active site forming salt bridge with Asp194.Catalytic Triad:Gly 193, Ser 195 and His 57.The amide nitrogen atoms of Gly 193 and Ser 195 form oxyanion hole. Oxyanion hole plays key role in stabilizing the negatively charged tetrahedral intermediate.
		+
		+	[[Image:FVIIa uninhibited.png\|left\|250px]]
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+
		+

Burcu Baykal at 09:41, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 09:41:09 GMT

←Older revision		Revision as of 09:41, 9 December 2008
Line 2:		Line 2:

	Secondary hemostasis is a complex system resulting fibrin formation as an output of the interaction between coagulation factors. Coagulation factors are serine proteases that forms coagulation cascade. It can be initiated via two different pathways: intrinsic and extrinsic.		Secondary hemostasis is a complex system resulting fibrin formation as an output of the interaction between coagulation factors. Coagulation factors are serine proteases that forms coagulation cascade. It can be initiated via two different pathways: intrinsic and extrinsic.
		+	[[Image:Cascade.jpg.png\|left\|100px]]

Burcu Baykal at 05:08, 9 December 2008

Burcu Baykal — Tue, 09 Dec 2008 05:08:04 GMT

←Older revision		Revision as of 05:08, 9 December 2008
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	<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>		<scene name='User:Burcu_Baykal/Sandbox1/Factor_viia/2'>TextToBeDisplayed</scene>
-	[[Image:Klj a.png\|left\|~~100px~~]]	+	[[Image:Klj a.png\|left\|400px]]