1zom: Difference between revisions
New page: left|200px<br /> <applet load="1zom" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zom, resolution 2.25Å" /> '''Crystal Structure o... |
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[[Image:1zom.gif|left|200px]]<br /> | [[Image:1zom.gif|left|200px]]<br /><applet load="1zom" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1zom, resolution 2.25Å" /> | caption="1zom, resolution 2.25Å" /> | ||
'''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor'''<br /> | '''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor'''<br /> | ||
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==Overview== | ==Overview== | ||
Human coagulation factor XIa (FXIa), a serine protease activated by, site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation, cascade. To investigate the potential of FXIa inhibitors as safe, anticoagulants, a series of potent, selective peptidomimetic inhibitors of, FXIa were designed and synthesized. Some of these inhibitors showed low, nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity and, >100-fold thrombin selectivity. The X-ray structure of one of these, inhibitors, 36, demonstrates its unique binding interactions with FXIa., Compound 32 caused a doubling of the activated partial thromboplastin time, in human plasma at 2.4 microM and was efficacious in a rat model of venous, thrombosis. These data suggest that factor XIa plays a significant role in, venous thrombosis and may be a suitable target for the development of, antithrombotic therapy. | Human coagulation factor XIa (FXIa), a serine protease activated by, site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation, cascade. To investigate the potential of FXIa inhibitors as safe, anticoagulants, a series of potent, selective peptidomimetic inhibitors of, FXIa were designed and synthesized. Some of these inhibitors showed low, nanomolar FXIa inhibitory activity with >1000-fold FXa selectivity and, >100-fold thrombin selectivity. The X-ray structure of one of these, inhibitors, 36, demonstrates its unique binding interactions with FXIa., Compound 32 caused a doubling of the activated partial thromboplastin time, in human plasma at 2.4 microM and was efficacious in a rat model of venous, thrombosis. These data suggest that factor XIa plays a significant role in, venous thrombosis and may be a suitable target for the development of, antithrombotic therapy. | ||
==About this Structure== | ==About this Structure== | ||
1ZOM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and 339 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] Full crystallographic information is available from [http:// | 1ZOM is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=339:'>339</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZOM OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: inhibitor]] | [[Category: inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:29:48 2008'' | ||
