1dan

Complex of active site inhibited human blood coagulation factor VIIA with human recombinant soluble tissue factor

Structural highlights

1dan is a 4 chain structure with sequence from Homo sapiens. The March 2006 RCSB PDB Molecule of the Month feature on Tissue Factor by David S. Goodsell is 10.2210/rcsb_pdb/mom_2006_3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	0Z6, BGC, CA, CAC, CGU, CL, FUC
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FA7_HUMAN Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:227500. A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20] ^[21] ^[22] ^[23] ^[24]

Function

FA7_HUMAN Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Blood coagulation is initiated when tissue factor binds to coagulation factor VIIa to give an enzymatically active complex which then activates factors IX and X, leading to thrombin generation and clot formation. We have determined the crystal structure at 2.0-A degrees resolution of active-site-inhibited factor VIIa complexed with the cleaved extracellular domain of tissue factor. In the complex, factor VIIa adopts an extended conformation. This structure provides a basis for understanding many molecular aspects of the initiation of coagulation.

The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor.,Banner DW, D'Arcy A, Chene C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D Nature. 1996 Mar 7;380(6569):41-6. PMID:8598903^[25]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bernardi F, Liney DL, Patracchini P, Gemmati D, Legnani C, Arcieri P, Pinotti M, Redaelli R, Ballerini G, Pemberton S, et al.. Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII. Br J Haematol. 1994 Mar;86(3):610-8. PMID:8043443
↑ O'Brien DP, Gale KM, Anderson JS, McVey JH, Miller GJ, Meade TW, Tuddenham EG. Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male. Blood. 1991 Jul 1;78(1):132-40. PMID:2070047
↑ Marchetti G, Patracchini P, Gemmati D, DeRosa V, Pinotti M, Rodorigo G, Casonato A, Girolami A, Bernardi F. Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7). Hum Genet. 1992 Jul;89(5):497-502. PMID:1634227
↑ Marchetti G, Ferrati M, Patracchini P, Redaelli R, Bernardi F. A missense mutation (178Cys-->Tyr) and two neutral dimorphisms (115His and 333Ser) in the human coagulation factor VII gene. Hum Mol Genet. 1993 Jul;2(7):1055-6. PMID:8364544
↑ Chaing S, Clarke B, Sridhara S, Chu K, Friedman P, VanDusen W, Roberts HR, Blajchman M, Monroe DM, High KA. Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor. Blood. 1994 Jun 15;83(12):3524-35. PMID:8204879
↑ Bernardi F, Castaman G, Redaelli R, Pinotti M, Lunghi B, Rodeghiero F, Marchetti G. Topologically equivalent mutations causing dysfunctional coagulation factors VII (294Ala-->Val) and X (334Ser-->Pro). Hum Mol Genet. 1994 Jul;3(7):1175-7. PMID:7981691
↑ Ohiwa M, Hayashi T, Wada H, Minamikawa K, Shirakawa S, Suzuki K. Factor VII Mie: homozygous asymptomatic type I deficiency caused by an amino acid substitution of His (CAC) for Arg(247) (CGC) in the catalytic domain. Thromb Haemost. 1994 Jun;71(6):773-7. PMID:7974346
↑ Arbini AA, Mannucci M, Bauer KA. A Thr359Met mutation in factor VII of a patient with a hereditary deficiency causes defective secretion of the molecule. Blood. 1996 Jun 15;87(12):5085-94. PMID:8652821
↑ Bernardi F, Castaman G, Pinotti M, Ferraresi P, Di Iasio MG, Lunghi B, Rodeghiero F, Marchetti G. Mutation pattern in clinically asymptomatic coagulation factor VII deficiency. Hum Mutat. 1996;8(2):108-15. PMID:8844208 doi:<108::AID-HUMU2>3.0.CO;2-7 10.1002/(SICI)1098-1004(1996)8:2<108::AID-HUMU2>3.0.CO;2-7
↑ Bharadwaj D, Iino M, Kontoyianni M, Smith KJ, Foster DC, Kisiel W. Factor VII central. A novel mutation in the catalytic domain that reduces tissue factor binding, impairs activation by factor Xa, and abolishes amidolytic and coagulant activity. J Biol Chem. 1996 Nov 29;271(48):30685-91. PMID:8940045
↑ Tamary H, Fromovich Y, Shalmon L, Reich Z, Dym O, Lanir N, Brenner B, Paz M, Luder AS, Blau O, Korostishevsky M, Zaizov R, Seligsohn U. Ala244Val is a common, probably ancient mutation causing factor VII deficiency in Moroccan and Iranian Jews. Thromb Haemost. 1996 Sep;76(3):283-91. PMID:8883260
↑ Leonard BJ, Chen Q, Blajchman MA, Ofosu FA, Sridhara S, Yang D, Clarke BJ. Factor VII deficiency caused by a structural variant N57D of the first epidermal growth factor domain. Blood. 1998 Jan 1;91(1):142-8. PMID:9414278
↑ Ozawa T, Takikawa Y, Niiya K, Ejiri N, Suzuki K, Sato S, Sakuragawa N. Factor VII Morioka (FVII L-26P): a homozygous missense mutation in the signal sequence identified in a patient with factor VII deficiency. Br J Haematol. 1998 Apr;101(1):47-9. PMID:9576180
↑ Alshinawi C, Scerri C, Galdies R, Aquilina A, Felice AE. Two new missense mutations (P134T and A244V) in the coagulation factor VII gene. Hum Mutat. 1998;Suppl 1:S189-91. PMID:9452082
↑ Au WY, Lam CC, Chan EC, Kwong YL. Two novel factor VII gene mutations in a Chinese family with factor VII deficiency. Br J Haematol. 2000 Oct;111(1):143-5. PMID:11091194
↑ Millar DS, Kemball-Cook G, McVey JH, Tuddenham EG, Mumford AD, Attock GB, Reverter JC, Lanir N, Parapia LA, Reynaud J, Meili E, von Felton A, Martinowitz U, Prangnell DR, Krawczak M, Cooper DN. Molecular analysis of the genotype-phenotype relationship in factor VII deficiency. Hum Genet. 2000 Oct;107(4):327-42. PMID:11129332
↑ Wulff K, Herrmann FH. Twenty two novel mutations of the factor VII gene in factor VII deficiency. Hum Mutat. 2000;15(6):489-96. PMID:10862079 doi:<489::AID-HUMU1>3.0.CO;2-J 10.1002/1098-1004(200006)15:6<489::AID-HUMU1>3.0.CO;2-J
↑ Nagaizumi K, Inaba H, Suzuki T, Hatta Y, Hagiwara T, Amano K, Arai M, Fukutake K. Two double heterozygous mutations in the F7 gene show different manifestations. Br J Haematol. 2002 Dec;119(4):1052-8. PMID:12472587
↑ Takamiya O, Hino K. A patient homozygous for a Gly354Cys mutation in factor VII that results in severely impaired secretion of the molecule, but not complete deficiency. Br J Haematol. 2004 Feb;124(3):336-42. PMID:14717781
↑ Mota L, Shetty S, Idicula-Thomas S, Ghosh K. Phenotypic and genotypic characterization of Factor VII deficiency patients from Western India. Clin Chim Acta. 2009 Nov;409(1-2):106-11. doi: 10.1016/j.cca.2009.09.007. Epub, 2009 Sep 13. PMID:19751712 doi:10.1016/j.cca.2009.09.007
↑ Herrmann FH, Wulff K, Auerswald G, Schulman S, Astermark J, Batorova A, Kreuz W, Pollmann H, Ruiz-Saez A, De Bosch N, Salazar-Sanchez L. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia. 2009 Jan;15(1):267-80. doi: 10.1111/j.1365-2516.2008.01910.x. Epub, 2008 Oct 30. PMID:18976247 doi:10.1111/j.1365-2516.2008.01910.x
↑ Landau D, Rosenberg N, Zivelin A, Staretz-Chacham O, Kapelushnik J. Familial factor VII deficiency with foetal and neonatal fatal cerebral haemorrhage associated with homozygosis to Gly180Arg mutation. Haemophilia. 2009 May;15(3):774-8. doi: 10.1111/j.1365-2516.2009.02004.x. PMID:19432927 doi:10.1111/j.1365-2516.2009.02004.x
↑ Kwon MJ, Yoo KY, Lee KO, Kim SH, Kim HJ. Recurrent mutations and genotype-phenotype correlations in hereditary factor VII deficiency in Korea. Blood Coagul Fibrinolysis. 2011 Mar;22(2):102-5. doi:, 10.1097/MBC.0b013e328343641a. PMID:21206266 doi:10.1097/MBC.0b013e328343641a
↑ Jiang M, Wang Z, Yu Z, Bai X, Su J, Cao L, Zhang W, Ruan C. A novel missense mutation close to the charge-stabilizing system in a patient with congenital factor VII deficiency. Blood Coagul Fibrinolysis. 2011 Jun;22(4):264-70. doi:, 10.1097/MBC.0b013e3283447388. PMID:21372693 doi:10.1097/MBC.0b013e3283447388
↑ Banner DW, D'Arcy A, Chene C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature. 1996 Mar 7;380(6569):41-6. PMID:8598903 doi:https://dx.doi.org/10.1038/380041a0

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Bernardi F, Liney DL, Patracchini P, Gemmati D, Legnani C, Arcieri P, Pinotti M, Redaelli R, Ballerini G, Pemberton S, et al.. Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII. Br J Haematol. 1994 Mar;86(3):610-8. PMID:8043443

[2] O'Brien DP, Gale KM, Anderson JS, McVey JH, Miller GJ, Meade TW, Tuddenham EG. Purification and characterization of factor VII 304-Gln: a variant molecule with reduced activity isolated from a clinically unaffected male. Blood. 1991 Jul 1;78(1):132-40. PMID:2070047

[3] Marchetti G, Patracchini P, Gemmati D, DeRosa V, Pinotti M, Rodorigo G, Casonato A, Girolami A, Bernardi F. Detection of two missense mutations and characterization of a repeat polymorphism in the factor VII gene (F7). Hum Genet. 1992 Jul;89(5):497-502. PMID:1634227

[4] Marchetti G, Ferrati M, Patracchini P, Redaelli R, Bernardi F. A missense mutation (178Cys-->Tyr) and two neutral dimorphisms (115His and 333Ser) in the human coagulation factor VII gene. Hum Mol Genet. 1993 Jul;2(7):1055-6. PMID:8364544

[5] Chaing S, Clarke B, Sridhara S, Chu K, Friedman P, VanDusen W, Roberts HR, Blajchman M, Monroe DM, High KA. Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor. Blood. 1994 Jun 15;83(12):3524-35. PMID:8204879

[6] Bernardi F, Castaman G, Redaelli R, Pinotti M, Lunghi B, Rodeghiero F, Marchetti G. Topologically equivalent mutations causing dysfunctional coagulation factors VII (294Ala-->Val) and X (334Ser-->Pro). Hum Mol Genet. 1994 Jul;3(7):1175-7. PMID:7981691

[7] Ohiwa M, Hayashi T, Wada H, Minamikawa K, Shirakawa S, Suzuki K. Factor VII Mie: homozygous asymptomatic type I deficiency caused by an amino acid substitution of His (CAC) for Arg(247) (CGC) in the catalytic domain. Thromb Haemost. 1994 Jun;71(6):773-7. PMID:7974346

[8] Arbini AA, Mannucci M, Bauer KA. A Thr359Met mutation in factor VII of a patient with a hereditary deficiency causes defective secretion of the molecule. Blood. 1996 Jun 15;87(12):5085-94. PMID:8652821

[9] Bernardi F, Castaman G, Pinotti M, Ferraresi P, Di Iasio MG, Lunghi B, Rodeghiero F, Marchetti G. Mutation pattern in clinically asymptomatic coagulation factor VII deficiency. Hum Mutat. 1996;8(2):108-15. PMID:8844208 doi:<108::AID-HUMU2>3.0.CO;2-7 10.1002/(SICI)1098-1004(1996)8:2<108::AID-HUMU2>3.0.CO;2-7

[10] Bharadwaj D, Iino M, Kontoyianni M, Smith KJ, Foster DC, Kisiel W. Factor VII central. A novel mutation in the catalytic domain that reduces tissue factor binding, impairs activation by factor Xa, and abolishes amidolytic and coagulant activity. J Biol Chem. 1996 Nov 29;271(48):30685-91. PMID:8940045

[11] Tamary H, Fromovich Y, Shalmon L, Reich Z, Dym O, Lanir N, Brenner B, Paz M, Luder AS, Blau O, Korostishevsky M, Zaizov R, Seligsohn U. Ala244Val is a common, probably ancient mutation causing factor VII deficiency in Moroccan and Iranian Jews. Thromb Haemost. 1996 Sep;76(3):283-91. PMID:8883260

[12] Leonard BJ, Chen Q, Blajchman MA, Ofosu FA, Sridhara S, Yang D, Clarke BJ. Factor VII deficiency caused by a structural variant N57D of the first epidermal growth factor domain. Blood. 1998 Jan 1;91(1):142-8. PMID:9414278

[13] Ozawa T, Takikawa Y, Niiya K, Ejiri N, Suzuki K, Sato S, Sakuragawa N. Factor VII Morioka (FVII L-26P): a homozygous missense mutation in the signal sequence identified in a patient with factor VII deficiency. Br J Haematol. 1998 Apr;101(1):47-9. PMID:9576180

[14] Alshinawi C, Scerri C, Galdies R, Aquilina A, Felice AE. Two new missense mutations (P134T and A244V) in the coagulation factor VII gene. Hum Mutat. 1998;Suppl 1:S189-91. PMID:9452082

[15] Au WY, Lam CC, Chan EC, Kwong YL. Two novel factor VII gene mutations in a Chinese family with factor VII deficiency. Br J Haematol. 2000 Oct;111(1):143-5. PMID:11091194

[16] Millar DS, Kemball-Cook G, McVey JH, Tuddenham EG, Mumford AD, Attock GB, Reverter JC, Lanir N, Parapia LA, Reynaud J, Meili E, von Felton A, Martinowitz U, Prangnell DR, Krawczak M, Cooper DN. Molecular analysis of the genotype-phenotype relationship in factor VII deficiency. Hum Genet. 2000 Oct;107(4):327-42. PMID:11129332

[17] Wulff K, Herrmann FH. Twenty two novel mutations of the factor VII gene in factor VII deficiency. Hum Mutat. 2000;15(6):489-96. PMID:10862079 doi:<489::AID-HUMU1>3.0.CO;2-J 10.1002/1098-1004(200006)15:6<489::AID-HUMU1>3.0.CO;2-J

[18] Nagaizumi K, Inaba H, Suzuki T, Hatta Y, Hagiwara T, Amano K, Arai M, Fukutake K. Two double heterozygous mutations in the F7 gene show different manifestations. Br J Haematol. 2002 Dec;119(4):1052-8. PMID:12472587

[19] Takamiya O, Hino K. A patient homozygous for a Gly354Cys mutation in factor VII that results in severely impaired secretion of the molecule, but not complete deficiency. Br J Haematol. 2004 Feb;124(3):336-42. PMID:14717781

[20] Mota L, Shetty S, Idicula-Thomas S, Ghosh K. Phenotypic and genotypic characterization of Factor VII deficiency patients from Western India. Clin Chim Acta. 2009 Nov;409(1-2):106-11. doi: 10.1016/j.cca.2009.09.007. Epub, 2009 Sep 13. PMID:19751712 doi:10.1016/j.cca.2009.09.007

[21] Herrmann FH, Wulff K, Auerswald G, Schulman S, Astermark J, Batorova A, Kreuz W, Pollmann H, Ruiz-Saez A, De Bosch N, Salazar-Sanchez L. Factor VII deficiency: clinical manifestation of 717 subjects from Europe and Latin America with mutations in the factor 7 gene. Haemophilia. 2009 Jan;15(1):267-80. doi: 10.1111/j.1365-2516.2008.01910.x. Epub, 2008 Oct 30. PMID:18976247 doi:10.1111/j.1365-2516.2008.01910.x

[22] Landau D, Rosenberg N, Zivelin A, Staretz-Chacham O, Kapelushnik J. Familial factor VII deficiency with foetal and neonatal fatal cerebral haemorrhage associated with homozygosis to Gly180Arg mutation. Haemophilia. 2009 May;15(3):774-8. doi: 10.1111/j.1365-2516.2009.02004.x. PMID:19432927 doi:10.1111/j.1365-2516.2009.02004.x

[23] Kwon MJ, Yoo KY, Lee KO, Kim SH, Kim HJ. Recurrent mutations and genotype-phenotype correlations in hereditary factor VII deficiency in Korea. Blood Coagul Fibrinolysis. 2011 Mar;22(2):102-5. doi:, 10.1097/MBC.0b013e328343641a. PMID:21206266 doi:10.1097/MBC.0b013e328343641a

[24] Jiang M, Wang Z, Yu Z, Bai X, Su J, Cao L, Zhang W, Ruan C. A novel missense mutation close to the charge-stabilizing system in a patient with congenital factor VII deficiency. Blood Coagul Fibrinolysis. 2011 Jun;22(4):264-70. doi:, 10.1097/MBC.0b013e3283447388. PMID:21372693 doi:10.1097/MBC.0b013e3283447388

[25] Banner DW, D'Arcy A, Chene C, Winkler FK, Guha A, Konigsberg WH, Nemerson Y, Kirchhofer D. The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor. Nature. 1996 Mar 7;380(6569):41-6. PMID:8598903 doi:https://dx.doi.org/10.1038/380041a0

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1dan

Complex of active site inhibited human blood coagulation factor VIIA with human recombinant soluble tissue factor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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