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'''Unreleased structure'''


The entry 4ibl is ON HOLD  until Apr 02 2015
==Rubidium Sites in Blood Coagulation Factor VIIa==
<StructureSection load='4ibl' size='340' side='right'caption='[[4ibl]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ibl]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IBL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IBL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ibl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ibl OCA], [https://pdbe.org/4ibl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ibl RCSB], [https://www.ebi.ac.uk/pdbsum/4ibl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ibl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[https://omim.org/entry/227500 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.<ref>PMID:8043443</ref> <ref>PMID:2070047</ref> <ref>PMID:1634227</ref> <ref>PMID:8364544</ref> <ref>PMID:8204879</ref> <ref>PMID:7981691</ref> <ref>PMID:7974346</ref> <ref>PMID:8652821</ref> <ref>PMID:8844208</ref> <ref>PMID:8940045</ref> <ref>PMID:8883260</ref> <ref>PMID:9414278</ref> <ref>PMID:9576180</ref> <ref>PMID:9452082</ref> <ref>PMID:11091194</ref> <ref>PMID:11129332</ref> <ref>PMID:10862079</ref> <ref>PMID:12472587</ref> <ref>PMID:14717781</ref> <ref>PMID:19751712</ref> <ref>PMID:18976247</ref> <ref>PMID:19432927</ref> <ref>PMID:21206266</ref> <ref>PMID:21372693</ref>
== Function ==
[https://www.uniprot.org/uniprot/FA7_HUMAN 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Coagulation factor VIIa (FVIIa) consists of a gamma-carboxyglutamic acid (GLA) domain, two epidermal growth factor-like (EGF) domains and a protease domain. FVIIa binds three Mg(2+) ions and four Ca(2+) ions in the GLA domain, one Ca(2+) ion in the EGF1 domain and one Ca(2+) ion in the protease domain. Further, FVIIa contains an Na(+) site in the protease domain. Since Na(+) and water share the same number of electrons, Na(+) sites in proteins are difficult to distinguish from waters in X-ray structures. Here, to verify the Na(+) site in FVIIa, the structure of the FVIIa-soluble tissue factor (TF) complex was solved at 1.8 A resolution containing Mg(2+), Ca(2+) and Rb(+) ions. In this structure, Rb(+) replaced two Ca(2+) sites in the GLA domain and occupied three non-metal sites in the protease domain. However, Rb(+) was not detected at the expected Na(+) site. In kinetic experiments, Na(+) increased the amidolytic activity of FVIIa towards the synthetic substrate S-2288 (H-D-Ile-Pro-Arg-p-nitroanilide) by approximately 20-fold; however, in the presence of Ca(2+), Na(+) had a negligible effect. Ca(2+) increased the hydrolytic activity of FVIIa towards S-2288 by approximately 60-fold in the absence of Na(+) and by approximately 82-fold in the presence of Na(+). In molecular-dynamics simulations, Na(+) stabilized the two Na(+)-binding loops (the 184-loop and 220-loop) and the TF-binding region spanning residues 163-180. Ca(2+) stabilized the Ca(2+)-binding loop (the 70-loop) and Na(+)-binding loops but not the TF-binding region. Na(+) and Ca(2+) together stabilized both the Na(+)-binding and Ca(2+)-binding loops and the TF-binding region. Previously, Rb(+) has been used to define the Na(+) site in thrombin; however, it was unsuccessful in detecting the Na(+) site in FVIIa. A conceivable explanation for this observation is provided.


Authors: Vadivel, K., Schmidt, A., Cascio, D., Padmanabhan, K., Bajaj, S.P.
Structure of human factor VIIa-soluble tissue factor with calcium, magnesium and rubidium.,Vadivel K, Schmidt AE, Cascio D, Padmanabhan K, Krishnaswamy S, Brandstetter H, Bajaj SP Acta Crystallogr D Struct Biol. 2021 Jun 1;77(Pt 6):809-819. doi:, 10.1107/S2059798321003922. Epub 2021 May 14. PMID:34076594<ref>PMID:34076594</ref>


Description: Rubidium Sites in Blood Coagulation Factor VIIa
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ibl" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
*[[Tissue factor|Tissue factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bajaj SP]]
[[Category: Cascio D]]
[[Category: Padmanabhan K]]
[[Category: Schmidt A]]
[[Category: Vadivel K]]

Latest revision as of 18:19, 20 September 2023

Rubidium Sites in Blood Coagulation Factor VIIaRubidium Sites in Blood Coagulation Factor VIIa

Structural highlights

4ibl is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:, , , , , , ,
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.

Publication Abstract from PubMed

Coagulation factor VIIa (FVIIa) consists of a gamma-carboxyglutamic acid (GLA) domain, two epidermal growth factor-like (EGF) domains and a protease domain. FVIIa binds three Mg(2+) ions and four Ca(2+) ions in the GLA domain, one Ca(2+) ion in the EGF1 domain and one Ca(2+) ion in the protease domain. Further, FVIIa contains an Na(+) site in the protease domain. Since Na(+) and water share the same number of electrons, Na(+) sites in proteins are difficult to distinguish from waters in X-ray structures. Here, to verify the Na(+) site in FVIIa, the structure of the FVIIa-soluble tissue factor (TF) complex was solved at 1.8 A resolution containing Mg(2+), Ca(2+) and Rb(+) ions. In this structure, Rb(+) replaced two Ca(2+) sites in the GLA domain and occupied three non-metal sites in the protease domain. However, Rb(+) was not detected at the expected Na(+) site. In kinetic experiments, Na(+) increased the amidolytic activity of FVIIa towards the synthetic substrate S-2288 (H-D-Ile-Pro-Arg-p-nitroanilide) by approximately 20-fold; however, in the presence of Ca(2+), Na(+) had a negligible effect. Ca(2+) increased the hydrolytic activity of FVIIa towards S-2288 by approximately 60-fold in the absence of Na(+) and by approximately 82-fold in the presence of Na(+). In molecular-dynamics simulations, Na(+) stabilized the two Na(+)-binding loops (the 184-loop and 220-loop) and the TF-binding region spanning residues 163-180. Ca(2+) stabilized the Ca(2+)-binding loop (the 70-loop) and Na(+)-binding loops but not the TF-binding region. Na(+) and Ca(2+) together stabilized both the Na(+)-binding and Ca(2+)-binding loops and the TF-binding region. Previously, Rb(+) has been used to define the Na(+) site in thrombin; however, it was unsuccessful in detecting the Na(+) site in FVIIa. A conceivable explanation for this observation is provided.

Structure of human factor VIIa-soluble tissue factor with calcium, magnesium and rubidium.,Vadivel K, Schmidt AE, Cascio D, Padmanabhan K, Krishnaswamy S, Brandstetter H, Bajaj SP Acta Crystallogr D Struct Biol. 2021 Jun 1;77(Pt 6):809-819. doi:, 10.1107/S2059798321003922. Epub 2021 May 14. PMID:34076594[25]

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

See Also

References

  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. ↑ Vadivel K, Schmidt AE, Cascio D, Padmanabhan K, Krishnaswamy S, Brandstetter H, Bajaj SP. Structure of human factor VIIa-soluble tissue factor with calcium, magnesium and rubidium. Acta Crystallogr D Struct Biol. 2021 Jun 1;77(Pt 6):809-819. doi:, 10.1107/S2059798321003922. Epub 2021 May 14. PMID:34076594 doi:http://dx.doi.org/10.1107/S2059798321003922

4ibl, resolution 1.80Å

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