1zom: Difference between revisions
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[[Image:1zom.gif|left|200px]] | [[Image:1zom.gif|left|200px]] | ||
'''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor''' | {{Structure | ||
|PDB= 1zom |SIZE=350|CAPTION= <scene name='initialview01'>1zom</scene>, resolution 2.25Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=339:(S)-2-(3-((R)-1-(4-BROMOPHENYL)ETHYL)UREIDO)-N-((S)-1-((S)-5-GUANIDINO-1-OXO-1-(THIAZOL-2-YL)PENTAN-2-YLAMINO)-3-METHYL-1-OXOBUTAN-2-YL)-5-UREIDOPENTANAMIDE'>339</scene> | |||
|ACTIVITY= [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] | |||
|GENE= F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1ZOM is a [ | 1ZOM is a [[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=1ZOM OCA]. | ||
==Reference== | ==Reference== | ||
Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants., Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, Rynkiewicz MJ, Gorga JC, Bibbins F, Celatka CA, Nagafuji P, Bannister TD, Meyers HV, Babine RE, Hayward NJ, Weaver D, Benjamin H, Stassen F, Abdel-Meguid SS, Strickler JE, J Med Chem. 2006 Dec 28;49(26):7781-91. PMID:[http:// | Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants., Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, Rynkiewicz MJ, Gorga JC, Bibbins F, Celatka CA, Nagafuji P, Bannister TD, Meyers HV, Babine RE, Hayward NJ, Weaver D, Benjamin H, Stassen F, Abdel-Meguid SS, Strickler JE, J Med Chem. 2006 Dec 28;49(26):7781-91. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17181160 17181160] | ||
[[Category: Coagulation factor XIa]] | [[Category: Coagulation factor XIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: inhibitor]] | [[Category: inhibitor]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:38:02 2008'' | ||
Revision as of 16:38, 20 March 2008
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| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | F11 (Homo sapiens) | ||||||
| Activity: | Coagulation factor XIa, with EC number 3.4.21.27 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the Catalytic Domain of Coagulation Factor XI in complex with a peptidomimetic Inhibitor
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[264900], Factor XI deficiency, autosomal recessive OMIM:[264900]
About this StructureAbout this Structure
1ZOM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Design, synthesis, and biological evaluation of peptidomimetic inhibitors of factor XIa as novel anticoagulants., Lin J, Deng H, Jin L, Pandey P, Quinn J, Cantin S, Rynkiewicz MJ, Gorga JC, Bibbins F, Celatka CA, Nagafuji P, Bannister TD, Meyers HV, Babine RE, Hayward NJ, Weaver D, Benjamin H, Stassen F, Abdel-Meguid SS, Strickler JE, J Med Chem. 2006 Dec 28;49(26):7781-91. PMID:17181160
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