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.


Antithrombin

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:58, 25 December 2019) (edit) (undo)
 
(25 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1tb6| PDB=1tb6 | SIZE=400| SCENE= |right|CAPTION=Antithrombin complex with thrombin and heparin polysaccharide, [[1tb6]] }}
+
<StructureSection load='3evj' size='350' side='right' caption='Glycosylated human antithrombin III complex with heparin (in green) (PDB code [[3evj]])' scene='46/466527/Cv/1'>
-
'''Antithrombin''' (AT) inactivates several enzymes of the coagulation cycle. α-AT contains 4 occupied glycosylation sites and is found in blood palsma. β-AT contains only 3 occupied glycosylation sites. AT-I refers to the absorption of thrombin to fibrin; AT-II and heparin interfere with the interactin of thrombin and fibrinogen; AT-III inactivates thrombin in plasma; AT-IV becomes activated during blood coagulation.
+
== Function ==
-
{{TOC limit|limit=2}}
+
'''Antithrombin''' (AT) inactivates several enzymes of the coagulation cycle. AT is relatively inactive until it binds the heparan sidechains of the microvasculature.<ref>PMID:15311269</ref><br />
 +
▪ '''α-AT''' contains 4 occupied glycosylation sites and is found in blood palsma.<br />
 +
▪ '''β-AT''' contains only 3 occupied glycosylation sites.<br />
 +
▪ '''AT-I''' refers to the absorption of thrombin to fibrin.<br />
 +
▪ '''AT-II''' and heparin interfere with the interaction of thrombin and fibrinogen.<br />
 +
▪ '''AT-III''' inactivates thrombin in plasma. For details see [[Student Projects for UMass Chemistry 423 Spring 2012-7|Student Projects for UMass Chemistry 423 Spring 2012-7 - Antithrombin III: Devourer of Memories]].<br />
 +
▪ '''AT-IV''' becomes activated during blood coagulation.<br />
 +
See details for the antithrombin pentasaccharide complex in [[Molecular Playground/Antithrombin-Heparin]].
-
==3D structures of antithrombin==
+
== Disease ==
-
[[1att]] – AT-III – bovine
+
AT deficiency diseases are: Acquired AT deficiency and Inherited AT deficiency. AT deficiency is involved in thrombosis and pulmonary embolism.
-
[[1ant]], [[2ant]] – hAT – human
+
== Relevance ==
 +
AT activity is enhanced upon <scene name='46/466527/Cv/4'>binding to the anticoagulant drug heparin</scene>.
-
[[1e05]] - hα-AT-III
+
==Structural highlights==
-
[[1e04]] – hβ-AT-III
+
The binding of AT to the heparans or the heparin drug is to a core pentasaccharide. The binding induces conformational change of AT.
-
[[1ath]], [[2znh]] – hAT-III
+
==3D structures of antithrombin==
-
 
+
[[Antithrombin 3D structures]]
-
[[1dzg]], [[1oyh]], [[1t1f]], [[2beh]], [[2b4x]], [[2hij]] - hAT-III (mutant)
+
-
 
+
-
===Antithrombin binary complexes===
+
-
 
+
-
[[1azx]], [[1nq9]], [[3evj]] – hAT + heparin pentasaccharide
+
-
 
+
-
[[1e03]] – hα-AT-III + heparin pentasaccharide
+
-
 
+
-
[[1dzh]] - hAT-III (mutant) + fluorescein
+
-
 
+
-
[[2gd4]] - hAT-III (mutant) + coagulation factor X
+
-
 
+
-
[[1br8]], [[1jvq]], [[1lk6]], [[1r1l]] – hAT-III + peptide
+
-
 
+
-
===Antithrombin ternary complexes===
+
-
 
+
-
[[1sr5]] - hAT-III + prothrombin + heparin heptasaccharide
+
-
 
+
-
[[1tb6]] - hAT-III (mutant) + thrombin + heparin polysaccharide
+
-
 
+
-
[[2b5t]] - AT-III (mutant) + thrombin (mutant) + heparin polysaccharide
+
-
[[3kcg]] - hAT-III (mutant) + coagulation factor IXa + heparin pentasaccharide
+
</StructureSection>
 +
== References ==
 +
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Glycosylated human antithrombin III complex with heparin (in green) (PDB code 3evj)

Drag the structure with the mouse to rotate

References

  1. ↑ Li W, Johnson DJ, Esmon CT, Huntington JA. Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004 Sep;11(9):857-62. Epub 2004 Aug 15. PMID:15311269 doi:10.1038/nsmb811

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Antithrombin"
Personal tools