2gd4: Difference between revisions
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New page: left|200px<br /> <applet load="2gd4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gd4, resolution 3.300Å" /> '''Crystal Structure ... |
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[[Image:2gd4.gif|left|200px]]<br /> | [[Image:2gd4.gif|left|200px]]<br /><applet load="2gd4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2gd4" size=" | |||
caption="2gd4, resolution 3.300Å" /> | caption="2gd4, resolution 3.300Å" /> | ||
'''Crystal Structure of the Antithrombin-S195A Factor Xa-Pentasaccharide Complex'''<br /> | '''Crystal Structure of the Antithrombin-S195A Factor Xa-Pentasaccharide Complex'''<br /> | ||
==Overview== | ==Overview== | ||
Regulation of blood coagulation is critical for maintaining blood flow, while preventing excessive bleeding or thrombosis. One of the principal | Regulation of blood coagulation is critical for maintaining blood flow, while preventing excessive bleeding or thrombosis. One of the principal regulatory mechanisms involves heparin activation of the serpin antithrombin (AT). Inhibition of several coagulation proteases is accelerated by up to 10,000-fold by heparin, either through bridging AT and the protease or by inducing allosteric changes in the properties of AT. The anticoagulant effect of short heparin chains, including the minimal AT-specific pentasaccharide, is mediated exclusively through the allosteric activation of AT towards efficient inhibition of coagulation factors (f) IXa and Xa. Here we present the crystallographic structure of the recognition (Michaelis) complex between heparin-activated AT and S195A fXa, revealing the extensive exosite contacts that confer specificity. The heparin-induced conformational change in AT is required to allow simultaneous contacts within the active site and two distinct exosites of fXa (36-loop and the autolysis loop). This structure explains the molecular basis of protease recognition by AT, and the mechanism of action of the important therapeutic low-molecular-weight heparins. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2GD4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, CA and NTO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http:// | 2GD4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=NTO:'>NTO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GD4 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Adams, T | [[Category: Adams, T E.]] | ||
[[Category: Huntington, J | [[Category: Huntington, J A.]] | ||
[[Category: Johnson, D | [[Category: Johnson, D J.]] | ||
[[Category: Li, W.]] | [[Category: Li, W.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: serpin]] | [[Category: serpin]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:30:33 2008'' | ||
