4e7r: Difference between revisions

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<StructureSection load='4e7r' size='340' side='right'caption='[[4e7r]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
<StructureSection load='4e7r' size='340' side='right'caption='[[4e7r]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4e7r]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E7R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E7R FirstGlance]. <br>
<table><tr><td colspan='2'>[[4e7r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E7R FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0NW:3-[(2S)-3-[4-(2-AMINOETHYL)PIPERIDIN-1-YL]-2-{[(2,4-DICHLOROBIPHENYL-3-YL)SULFONYL]AMINO}-3-OXOPROPYL]BENZENECARBOXIMIDAMIDE'>0NW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0NW:3-[(2S)-3-[4-(2-AMINOETHYL)PIPERIDIN-1-YL]-2-{[(2,4-DICHLOROBIPHENYL-3-YL)SULFONYL]AMINO}-3-OXOPROPYL]BENZENECARBOXIMIDAMIDE'>0NW</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</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=4e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e7r OCA], [https://pdbe.org/4e7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e7r RCSB], [https://www.ebi.ac.uk/pdbsum/4e7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e7r ProSAT]</span></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qx5|3qx5]], [[3qwc|3qwc]], [[3f68|3f68]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </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=4e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e7r OCA], [http://pdbe.org/4e7r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e7r RCSB], [http://www.ebi.ac.uk/pdbsum/4e7r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e7r ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref>  Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 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.<ref>PMID:15534175</ref>  Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.  Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. 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.<ref>PMID:11506076</ref>
[[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref>  Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 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.<ref>PMID:15534175</ref>  Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.  Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]]. 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.<ref>PMID:11506076</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref> [[http://www.uniprot.org/uniprot/HIRV2_HIRME HIRV2_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.
[[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>  


==See Also==
==See Also==
*[[Hirudin|Hirudin]]
*[[Hirudin 3D structures|Hirudin 3D structures]]
*[[Thrombin|Thrombin]]
*[[Thrombin 3D Structures|Thrombin 3D Structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Hirudo medicinalis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Thrombin]]
[[Category: Heine A]]
[[Category: Heine, A]]
[[Category: Klebe G]]
[[Category: Klebe, G]]
[[Category: Ruehmann E]]
[[Category: Ruehmann, E]]
[[Category: Blood]]
[[Category: Blood clotting]]
[[Category: Blood clotting inhibitor]]
[[Category: Blood coagulation]]
[[Category: Convertion of fibrinogen to fibrin]]
[[Category: Glycosylation]]
[[Category: Hydrolase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Kringle]]
[[Category: Serine protease]]
[[Category: Thrombin inhibitor]]

Revision as of 09:55, 28 September 2022

Thrombin in complex with 3-amidinophenylalanine inhibitorThrombin in complex with 3-amidinophenylalanine inhibitor

Structural highlights

4e7r is a 6 chain structure with sequence from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Genetic variations in F2 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.[13] Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:614390]. 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.[14]

Function

[THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.[15]

See Also

References

  1. ↑ Wang W, Fu Q, Zhou R, Wu W, Ding Q, Hu Y, Wang X, Wang H, Wang Z. Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by Gly. Haemophilia. 2004 Jan;10(1):94-7. PMID:14962227
  2. ↑ Board PG, Shaw DC. Determination of the amino acid substitution in human prothrombin type 3 (157 Glu leads to Lys) and the localization of a third thrombin cleavage site. Br J Haematol. 1983 Jun;54(2):245-54. PMID:6405779
  3. ↑ Rabiet MJ, Furie BC, Furie B. Molecular defect of prothrombin Barcelona. Substitution of cysteine for arginine at residue 273. J Biol Chem. 1986 Nov 15;261(32):15045-8. PMID:3771562
  4. ↑ Miyata T, Morita T, Inomoto T, Kawauchi S, Shirakami A, Iwanaga S. Prothrombin Tokushima, a replacement of arginine-418 by tryptophan that impairs the fibrinogen clotting activity of derived thrombin Tokushima. Biochemistry. 1987 Feb 24;26(4):1117-22. PMID:3567158
  5. ↑ Inomoto T, Shirakami A, Kawauchi S, Shigekiyo T, Saito S, Miyoshi K, Morita T, Iwanaga S. Prothrombin Tokushima: characterization of dysfunctional thrombin derived from a variant of human prothrombin. Blood. 1987 Feb;69(2):565-9. PMID:3801671
  6. ↑ Henriksen RA, Mann KG. Identification of the primary structural defect in the dysthrombin thrombin Quick I: substitution of cysteine for arginine-382. Biochemistry. 1988 Dec 27;27(26):9160-5. PMID:3242619
  7. ↑ Henriksen RA, Mann KG. Substitution of valine for glycine-558 in the congenital dysthrombin thrombin Quick II alters primary substrate specificity. Biochemistry. 1989 Mar 7;28(5):2078-82. PMID:2719946
  8. ↑ Miyata T, Aruga R, Umeyama H, Bezeaud A, Guillin MC, Iwanaga S. Prothrombin Salakta: substitution of glutamic acid-466 by alanine reduces the fibrinogen clotting activity and the esterase activity. Biochemistry. 1992 Aug 25;31(33):7457-62. PMID:1354985
  9. ↑ Morishita E, Saito M, Kumabashiri I, Asakura H, Matsuda T, Yamaguchi K. Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His). Blood. 1992 Nov 1;80(9):2275-80. PMID:1421398
  10. ↑ Iwahana H, Yoshimoto K, Shigekiyo T, Shirakami A, Saito S, Itakura M. Detection of a single base substitution of the gene for prothrombin Tokushima. The application of PCR-SSCP for the genetic and molecular analysis of dysprothrombinemia. Int J Hematol. 1992 Feb;55(1):93-100. PMID:1349838
  11. ↑ James HL, Kim DJ, Zheng DQ, Girolami A. Prothrombin Padua I: incomplete activation due to an amino acid substitution at a factor Xa cleavage site. Blood Coagul Fibrinolysis. 1994 Oct;5(5):841-4. PMID:7865694
  12. ↑ Degen SJ, McDowell SA, Sparks LM, Scharrer I. Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala. Thromb Haemost. 1995 Feb;73(2):203-9. PMID:7792730
  13. ↑ 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
  14. ↑ Pihusch R, Buchholz T, Lohse P, Rubsamen H, Rogenhofer N, Hasbargen U, Hiller E, Thaler CJ. Thrombophilic gene mutations and recurrent spontaneous abortion: prothrombin mutation increases the risk in the first trimester. Am J Reprod Immunol. 2001 Aug;46(2):124-31. PMID:11506076
  15. ↑ Glenn KC, Frost GH, Bergmann JS, Carney DH. Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis. Pept Res. 1988 Nov-Dec;1(2):65-73. PMID:2856554

4e7r, resolution 2.25Å

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