1oph: Difference between revisions
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'''NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN'''<br /> | '''NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1OPH is a [http://en.wikipedia.org/wiki/Protein_complex 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]. Active as [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] Full crystallographic information is available from [http:// | 1OPH is a [http://en.wikipedia.org/wiki/Protein_complex 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]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OPH OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: trypsin]] | [[Category: trypsin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:34:56 2008'' | ||
Revision as of 17:34, 15 February 2008
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NON-COVALENT COMPLEX BETWEEN ALPHA-1-PI-PITTSBURGH AND S195A TRYPSIN
OverviewOverview
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.
DiseaseDisease
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 StructureAbout this Structure
1OPH is a Protein complex structure of sequences from Bos taurus and Homo sapiens. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
ReferenceReference
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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