1oph
From Proteopedia
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| - | [[Image:1oph.jpg|left|200px]] | + | [[Image:1oph.jpg|left|200px]] |
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| - | '''NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN''' | + | {{Structure |
| + | |PDB= 1oph |SIZE=350|CAPTION= <scene name='initialview01'>1oph</scene>, resolution 2.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] | ||
| + | |GENE= SERPINA1 OR PI OR AAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1OPH is a [ | + | 1OPH is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OPH OCA]. |
==Reference== | ==Reference== | ||
| - | Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases., Dementiev A, Simonovic M, Volz K, Gettins PG, J Biol Chem. 2003 Sep 26;278(39):37881-7. Epub 2003 Jul 14. PMID:[http:// | + | Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases., Dementiev A, Simonovic M, Volz K, Gettins PG, J Biol Chem. 2003 Sep 26;278(39):37881-7. Epub 2003 Jul 14. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12860985 12860985] |
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: trypsin]] | [[Category: trypsin]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:14:04 2008'' |
Revision as of 11:14, 20 March 2008
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| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | SERPINA1 OR PI OR AAT (Homo sapiens) | ||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN
Contents |
Overview
The serpin antithrombin is a slow thrombin inhibitor that requires heparin to enhance its reaction rate. In contrast, alpha1-proteinase inhibitor (alpha1PI) Pittsburgh (P1 Met --> Arg natural variant) inhibits thrombin 17 times faster than pentasaccharide heparin-activated antithrombin. We present here x-ray structures of free and S195A trypsin-bound alpha1PI Pittsburgh, which show that the reactive center loop (RCL) possesses a canonical conformation in the free serpin that does not change upon binding to S195A trypsin and that contacts the proteinase only between P2 and P2'. By inference from the structure of heparin cofactor II bound to S195A thrombin, this RCL conformation is also appropriate for binding to thrombin. Reaction rates of trypsin and thrombin with alpha1PI Pittsburgh and antithrombin and their P2 variants show that the low antithrombin-thrombin reaction rate results from the antithrombin RCL sequence at P2 and implies that, in solution, the antithrombin RCL must be in a similar canonical conformation to that found here for alpha1PI Pittsburgh, even in the nonheparin-activated state. This suggests a general, limited, canonical-like interaction between serpins and proteinases in their Michaelis complexes.
Disease
Known diseases associated with this structure: Emphysema OMIM:[107400], Emphysema-cirrhosis OMIM:[107400], Hemorrhagic diathesis due to antithrombin Pittsburgh OMIM:[107400], Pulmonary disease, chronic obstructive, susceptibility to OMIM:[107400]
About this Structure
1OPH is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases., Dementiev A, Simonovic M, Volz K, Gettins PG, J Biol Chem. 2003 Sep 26;278(39):37881-7. Epub 2003 Jul 14. PMID:12860985
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