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Antithrombin

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{{STRUCTURE_1tb6| PDB=1tb6 | SIZE=400| SCENE= |right|CAPTION=Antithrombin (beige) complex with thrombin heavy chain (pink), light chain (green) and heparin polysaccharide, [[1tb6]] }}
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<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'>
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'''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 interaction of thrombin and fibrinogen; AT-III inactivates thrombin in plasma; AT-IV becomes activated during blood coagulation. See details for the antithrombin pentasaccharide complex in [[Molecular Playground/antithrombin-Heparin]].
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== Function ==
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__NOTOC__
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'''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 />
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▪ '''α-AT''' contains 4 occupied glycosylation sites and is found in blood palsma.<br />
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▪ '''β-AT''' contains only 3 occupied glycosylation sites.<br />
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▪ '''AT-I''' refers to the absorption of thrombin to fibrin.<br />
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▪ '''AT-II''' and heparin interfere with the interaction of thrombin and fibrinogen.<br />
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▪ '''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 />
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▪ '''AT-IV''' becomes activated during blood coagulation.<br />
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See details for the antithrombin pentasaccharide complex in [[Molecular Playground/Antithrombin-Heparin]].
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==3D structures of antithrombin==
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== Disease ==
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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AT deficiency diseases are: Acquired AT deficiency and Inherited AT deficiency. AT deficiency is involved in thrombosis and pulmonary embolism.
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{{#tree:id=OrganizedByTopic|openlevels=0|
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*Antithrombin
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== Relevance ==
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AT activity is enhanced upon <scene name='46/466527/Cv/4'>binding to the anticoagulant drug heparin</scene>.
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**[[1att]] – AT-III – bovine
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==Structural highlights==
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**[[1ant]], [[2ant]] – hAT – human
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The binding of AT to the heparans or the heparin drug is to a core pentasaccharide. The binding induces conformational change of AT.
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**[[1e05]] - hα-AT-III
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==3D structures of antithrombin==
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[[Antithrombin 3D structures]]
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**[[1e04]] – hβ-AT-III
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**[[1ath]], [[2znh]], [[4eb1]] – hAT-III
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**[[1dzg]], [[1oyh]], [[1t1f]], [[2beh]], [[2b4x]], [[2hij]] - hAT-III (mutant)
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*Antithrombin binary complexes
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**[[1azx]], [[1nq9]], [[3evj]] – hAT + heparin pentasaccharide
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**[[1e03]] – hα-AT-III + heparin pentasaccharide
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**[[1dzh]] - hAT-III (mutant) + fluorescein
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**[[2gd4]] - hAT-III (mutant) + coagulation factor X
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**[[1br8]], [[1jvq]], [[1lk6]], [[1r1l]] – hAT-III + peptide
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*Antithrombin ternary complexes
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**[[1sr5]] - hAT-III + prothrombin + heparin heptasaccharide
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**[[1tb6]] - hAT-III (mutant) + thrombin + heparin polysaccharide
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**[[2b5t]] - AT-III (mutant) + thrombin (mutant) + heparin polysaccharide
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</StructureSection>
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**[[3kcg]] - hAT-III (mutant) + coagulation factor IXa + heparin pentasaccharide
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== References ==
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}}
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<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

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