1sr5

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[[Image:1sr5.jpg|left|200px]]<br /><applet load="1sr5" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1sr5.jpg|left|200px]]
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caption="1sr5, resolution 3.10&Aring;" />
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'''ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE'''<br />
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{{Structure
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|PDB= 1sr5 |SIZE=350|CAPTION= <scene name='initialview01'>1sr5</scene>, resolution 3.10&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NT1:HEPARIN+HEPTASACCHARIDE'>NT1</scene> and <scene name='pdbligand=NT2:2,3,4,6-TETRA-O-SULFOHEXOPYRANOSE'>NT2</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1SR5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NT1:'>NT1</scene> and <scene name='pdbligand=NT2:'>NT2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SR5 OCA].
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1SR5 is a [[Protein complex]] structure of sequences 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=1SR5 OCA].
==Reference==
==Reference==
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The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity., Dementiev A, Petitou M, Herbert JM, Gettins PG, Nat Struct Mol Biol. 2004 Sep;11(9):863-7. Epub 2004 Aug 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15311268 15311268]
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The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity., Dementiev A, Petitou M, Herbert JM, Gettins PG, Nat Struct Mol Biol. 2004 Sep;11(9):863-7. Epub 2004 Aug 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15311268 15311268]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: NT2]]
[[Category: NT2]]
[[Category: antithrombin activation by hep anhydrothrombin]]
[[Category: antithrombin activation by hep anhydrothrombin]]
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[[Category: protein-protein interactions]]
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[[Category: protein-protein interaction]]
[[Category: serine proteinase inhibitor]]
[[Category: serine proteinase inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:04:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:08:37 2008''

Revision as of 12:08, 20 March 2008


PDB ID 1sr5

Drag the structure with the mouse to rotate
, resolution 3.10Å
Ligands: , and
Activity: Thrombin, with EC number 3.4.21.5
Coordinates: save as pdb, mmCIF, xml



ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE


Contents

Overview

Antithrombin, the principal physiological inhibitor of the blood coagulation proteinase thrombin, requires heparin as a cofactor. We report the crystal structure of the rate-determining encounter complex formed between antithrombin, anhydrothrombin and an optimal synthetic 16-mer oligosaccharide. The antithrombin reactive center loop projects from the serpin body and adopts a canonical conformation that makes extensive backbone and side chain contacts from P5 to P6' with thrombin's restrictive specificity pockets, including residues in the 60-loop. These contacts rationalize many earlier mutagenesis studies on thrombin specificity. The 16-mer oligosaccharide is just long enough to form the predicted bridge between the high-affinity pentasaccharide-binding site on antithrombin and the highly basic exosite 2 on thrombin, validating the design strategy for this synthetic heparin. The protein-protein and protein-oligosaccharide interactions together explain the basis for heparin activation of antithrombin as a thrombin inhibitor.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1SR5 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity., Dementiev A, Petitou M, Herbert JM, Gettins PG, Nat Struct Mol Biol. 2004 Sep;11(9):863-7. Epub 2004 Aug 15. PMID:15311268

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