This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1czv

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:29, 6 December 2017

CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: DIMERIC CRYSTAL FORM

Structural highlights

1czv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1czs, 1czt
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FA5_HUMAN] Defects in F5 are the cause of factor V deficiency (FA5D) [MIM:227400]; also known as Owren parahemophilia. It is a hemorrhagic diastesis.^[1] ^[2] Defects in F5 are the cause of thrombophilia due to activated protein C resistance (THPH2) [MIM:188055]. THPH2 is a hemostatic disorder due to defective degradation of factor Va by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis.^[3] ^[4] ^[5] ^[6] ^[7] Defects in F5 are a cause of susceptibility to Budd-Chiari syndrome (BDCHS) [MIM:600880]. A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. Defects in F5 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.^[8] Defects in F5 are associated with susceptibility to pregnancy loss, recurrent, type 1 (RPRGL1) [MIM:614389]. RPRGL1 is a common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.^[9]

Function

[FA5_HUMAN] Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.

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

Rapid and controlled clot formation is achieved through sequential activation of circulating serine proteinase precursors on phosphatidylserine-rich procoagulant membranes of activated platelets and endothelial cells. The homologous complexes Xase and prothrombinase, each consisting of an active proteinase and a non-enzymatic cofactor, perform critical steps within this coagulation cascade. The activated cofactors VIIIa and Va, highly specific for their cognate proteinases, are each derived from precursors with the same A1-A2-B-A3-C1-C2 architecture. Membrane binding is mediated by the C2 domains of both cofactors. Here we report two crystal structures of the C2 domain of human factor Va. The conserved beta-barrel framework provides a scaffold for three protruding loops, one of which adopts markedly different conformations in the two crystal forms. We propose a mechanism of calcium-independent, stereospecific binding of factors Va and VIIIa to phospholipid membranes, on the basis of (1) immersion of hydrophobic residues at the apices of these loops in the apolar membrane core; (2) specific interactions with phosphatidylserine head groups in the groove enclosed by these loops; and (3) favourable electrostatic contacts of basic side chains with negatively charged membrane phosphate groups.

Crystal structures of the membrane-binding C2 domain of human coagulation factor V.,Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P Nature. 1999 Nov 25;402(6760):434-9. PMID:10586886^[10]

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

References

↑ Castoldi E, Simioni P, Kalafatis M, Lunghi B, Tormene D, Girelli D, Girolami A, Bernardi F. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family. Blood. 2000 Aug 15;96(4):1443-8. PMID:10942390
↑ Duga S, Montefusco MC, Asselta R, Malcovati M, Peyvandi F, Santagostino E, Mannucci PM, Tenchini ML. Arg2074Cys missense mutation in the C2 domain of factor V causing moderately severe factor V deficiency: molecular characterization by expression of the recombinant protein. Blood. 2003 Jan 1;101(1):173-7. Epub 2002 Aug 15. PMID:12393490 doi:10.1182/blood-2002-06-1928
↑ Williamson D, Brown K, Luddington R, Baglin C, Baglin T. Factor V Cambridge: a new mutation (Arg306-->Thr) associated with resistance to activated protein C. Blood. 1998 Feb 15;91(4):1140-4. PMID:9454742
↑ van Wijk R, Nieuwenhuis K, van den Berg M, Huizinga EG, van der Meijden BB, Kraaijenhagen RJ, van Solinge WW. Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency. Blood. 2001 Jul 15;98(2):358-67. PMID:11435304
↑ Schrijver I, Houissa-Kastally R, Jones CD, Garcia KC, Zehnder JL. Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding. Thromb Haemost. 2002 Feb;87(2):294-9. PMID:11858490
↑ Mumford AD, McVey JH, Morse CV, Gomez K, Steen M, Norstrom EA, Tuddenham EG, Dahlback B, Bolton-Maggs PH. Factor V I359T: a novel mutation associated with thrombosis and resistance to activated protein C. Br J Haematol. 2003 Nov;123(3):496-501. PMID:14617013
↑ Steen M, Norstrom EA, Tholander AL, Bolton-Maggs PH, Mumford A, McVey JH, Tuddenham EG, Dahlback B. Functional characterization of factor V-Ile359Thr: a novel mutation associated with thrombosis. Blood. 2004 May 1;103(9):3381-7. Epub 2003 Dec 24. PMID:14695241 doi:10.1182/blood-2003-06-2092
↑ Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol. 2004 Nov;61(11):1652-61. PMID:15534175 doi:61/11/1652
↑ Martinelli I, Taioli E, Cetin I, Marinoni A, Gerosa S, Villa MV, Bozzo M, Mannucci PM. Mutations in coagulation factors in women with unexplained late fetal loss. N Engl J Med. 2000 Oct 5;343(14):1015-8. PMID:11018168 doi:10.1056/NEJM200010053431405
↑ Macedo-Ribeiro S, Bode W, Huber R, Quinn-Allen MA, Kim SW, Ortel TL, Bourenkov GP, Bartunik HD, Stubbs MT, Kane WH, Fuentes-Prior P. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature. 1999 Nov 25;402(6760):434-9. PMID:10586886 doi:10.1038/46594

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1czv"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: DIMERIC CRYSTAL FORM==
 <StructureSection load='1czv' size='340' side='right' caption='[[1czv]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1czv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CZV FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1czs|1czs]], [[1czt|1czt]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1czv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1czv OCA], [http://pdbe.org/1czv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1czv RCSB], [http://www.ebi.ac.uk/pdbsum/1czv PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1czv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1czv OCA], [http://pdbe.org/1czv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1czv RCSB], [http://www.ebi.ac.uk/pdbsum/1czv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1czv ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cz/1czv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cz/1czv_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1czv

From Proteopedia

Revision as of 08:29, 6 December 2017

CRYSTAL STRUCTURE OF THE C2 DOMAIN OF HUMAN COAGULATION FACTOR V: DIMERIC CRYSTAL FORM

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox