1sr5
From Proteopedia
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|PDB= 1sr5 |SIZE=350|CAPTION= <scene name='initialview01'>1sr5</scene>, resolution 3.10Å | |PDB= 1sr5 |SIZE=350|CAPTION= <scene name='initialview01'>1sr5</scene>, resolution 3.10Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NT1:HEPARIN+HEPTASACCHARIDE'>NT1</scene> | + | |LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NT1:HEPARIN+HEPTASACCHARIDE'>NT1</scene>, <scene name='pdbligand=NT2:2,3,4,6-TETRA-O-SULFOHEXOPYRANOSE'>NT2</scene> |
| - | |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] | + | |ACTIVITY= <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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sr5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sr5 OCA], [http://www.ebi.ac.uk/pdbsum/1sr5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sr5 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Gettins, P G.]] | [[Category: Gettins, P G.]] | ||
[[Category: Petitou, M.]] | [[Category: Petitou, M.]] | ||
| - | [[Category: NAG]] | ||
| - | [[Category: NT1]] | ||
| - | [[Category: NT2]] | ||
[[Category: antithrombin activation by hep anhydrothrombin]] | [[Category: antithrombin activation by hep anhydrothrombin]] | ||
[[Category: protein-protein interaction]] | [[Category: protein-protein interaction]] | ||
[[Category: serine proteinase inhibitor]] | [[Category: serine proteinase inhibitor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:45:56 2008'' |
Revision as of 20:45, 30 March 2008
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| , resolution 3.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE
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.
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
Page seeded by OCA on Sun Mar 30 23:45:56 2008
