1ant
From Proteopedia
(New page: 200px<br /> <applet load="1ant" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ant, resolution 3.0Å" /> '''BIOLOGICAL IMPLICATI...) |
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caption="1ant, resolution 3.0Å" /> | caption="1ant, resolution 3.0Å" /> | ||
'''BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN'''<br /> | '''BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ANT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1ANT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ANT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine protease inhibitor]] | [[Category: serine protease inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:29:28 2008'' |
Revision as of 13:29, 15 February 2008
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BIOLOGICAL IMPLICATIONS OF A 3 ANGSTROMS STRUCTURE OF DIMERIC ANTITHROMBIN
Overview
BACKGROUND: Antithrombin, a member of the serpin family of inhibitors, controls coagulation in human plasma by forming complexes with thrombin, and other coagulation proteases in a process greatly accelerated by, heparin. The structures of several serpins have been determined but not in, their active conformations. We have determined the structure of intact, antithrombin in order to study its mechanism of activation, particularly, with respect to heparin, and the dysfunctions of this mechanism that, predispose individuals to thrombotic disease. RESULTS: The crystal, structure of a dimer of one active and one inactive molecule of, antithrombin has been determined at 3 A. The first molecule has its, reactive-centre loop in a predicted active conformation compatible with, initial entry of two residues into the main beta-sheet of the molecule., The inactive molecule has a totally incorporated loop as in latent, plasminogen activator inhibitor-1. The two molecules are linked by the, reactive loop of the active molecule which has replaced a strand from, another beta-sheet in the latent molecule. CONCLUSION: The structure, together with identified mutations affecting its heparin affinity, allows, the placement of the heparin-binding site on the molecule. The, conformation of the two forms of antithrombin demonstrates the, extraordinary mobility of the reactive loop in the serpins and provides, insights into the folding of the loop required for inhibitory activity, together with the potential modification of this by heparin. The mechanism, of dimerization is relevant to the polymerization that is observed in, diseases associated with variant serpins.
About this Structure
1ANT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Biological implications of a 3 A structure of dimeric antithrombin., Carrell RW, Stein PE, Fermi G, Wardell MR, Structure. 1994 Apr 15;2(4):257-70. PMID:8087553
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