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1oo8

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[[Image:1oo8.gif|left|200px]]
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{{STRUCTURE_1oo8| PDB=1oo8 | SCENE= }}
{{STRUCTURE_1oo8| PDB=1oo8 | SCENE= }}
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'''CRYSTAL STRUCTURE OF A1PI-PITTSBURGH IN THE NATIVE CONFORMATION'''
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===CRYSTAL STRUCTURE OF A1PI-PITTSBURGH IN THE NATIVE CONFORMATION===
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==Overview==
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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 --&gt; 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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12860985 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12860985}}
==About this Structure==
==About this Structure==
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[[Category: Pittsburgh variant]]
[[Category: Pittsburgh variant]]
[[Category: Serpin]]
[[Category: Serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:05:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:31:57 2008''

Revision as of 09:31, 28 July 2008

Image:1oo8.png

Template:STRUCTURE 1oo8

CRYSTAL STRUCTURE OF A1PI-PITTSBURGH IN THE NATIVE CONFORMATION

Template:ABSTRACT PUBMED 12860985

About this Structure

1OO8 is a Single protein structure of sequence from 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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