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1a0h

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[[Image:1a0h.gif|left|200px]]
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==Overview==
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{{ABSTRACT_9438869}}
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BACKGROUND: The conversion of prothrombin to thrombin by factor Xa is the penultimate step in the blood clotting cascade. In vivo, where the conversion occurs primarily on activated platelets in association with factor Va and Ca2+ ions, meizothrombin is the major intermediate of the two step reaction. Meizothrombin rapidly loses the fragment 1 domain (F1) by autolysis to become meizothrombin des F1 (mzTBN-F1). The physiological properties of mzTBN-F1 differ dramatically from those of thrombin due to the presence of prothrombin fragment 2 (F2), which remains covalently attached to the activated thrombin domain in mzTBN-F1. RESULTS: The crystal structure of mzTBN-F1 has been determined at 3.1 A resolution by molecular replacement, using only the thrombin domain, and refined to R and Rfree values of 0.205 and 0.242, respectively. The protease active site was inhibited with D-Phe-Pro-Arg-chloromethylketone (PPACK) to reduce autolysis. The mobile linker chain connecting the so-called kringle and thrombin domains and the first two N-acetylglucosamine residues attached to the latter were seen in electron-density maps improved with the program SQUASH. Previously these regions had only been modeled. CONCLUSIONS: The F2 kringle domain in mzTBN-F1 is bound to the electropositive heparin-binding site on thrombin in an orientation that is systematically shifted and has significantly more interdomain contacts compared to a noncovalent complex of free F2 and free thrombin. F2 in mzTBN-F1 forms novel hydrogen bonds to the carbohydrate chain of thrombin and perhaps stabilizes a unique, rigid conformation of the gamma-autolysis loop through non-local effects. The F2 linker chain, which does not interfere with the active site or fibrinogen-recognition site, is arranged so that the two sites cleaved by factor Xa are separated by 36 A. The two mzTBN-F1 molecules in the asymmetric unit share a tight 'dimer' contact in which the active site of one molecule is partially blocked by the F2 kringle domain of its partner. This interaction suggests a new model for prothrombin organization.
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==About this Structure==
==About this Structure==
1A0H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The following page contains interesting information on the relation of 1A0H with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb25_1.html Thrombin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A0H OCA].
1A0H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The following page contains interesting information on the relation of 1A0H with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb25_1.html Thrombin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A0H OCA].
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==Reference==
 
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New insights into the regulation of the blood clotting cascade derived from the X-ray crystal structure of bovine meizothrombin des F1 in complex with PPACK., Martin PD, Malkowski MG, Box J, Esmon CT, Edwards BF, Structure. 1997 Dec 15;5(12):1681-93. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9438869 9438869]
 
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Serine protease]]
[[Category: Serine protease]]
[[Category: Thrombin]]
[[Category: Thrombin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:37:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:01:24 2008''

Revision as of 14:01, 26 June 2008

Image:1a0h.png

Template:STRUCTURE 1a0h

THE X-RAY CRYSTAL STRUCTURE OF PPACK-MEIZOTHROMBIN DESF1: KRINGLE/THROMBIN AND CARBOHYDRATE/KRINGLE/THROMBIN INTERACTIONS AND LOCATION OF THE LINKER CHAIN


Template:ABSTRACT 9438869

About this Structure

1A0H is a Single protein structure of sequence from Bos taurus. The following page contains interesting information on the relation of 1A0H with [Thrombin]. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 17:01:24 2008

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