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==Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor== | |||
<StructureSection load='4a7i' size='340' side='right' caption='[[4a7i]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4a7i]] is a 2 chain structure with 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=4A7I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A7I FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A7I:5-CHLORO-THIOPHENE-2-CARBOXYLIC+ACID+[2-(1--ISOPROPYL-PIPERIDIN-4-YLSULFAMOYL)-ETHYL]-AMIDE'>A7I</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | ||
[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref><ref>PMID:1973167</ref><ref>PMID:1985698</ref><ref>PMID:7669671</ref><ref>PMID:8529633</ref><ref>PMID:7860069</ref><ref>PMID:8845463</ref><ref>PMID:8910490</ref><ref>PMID:10468877</ref><ref>PMID:10746568</ref><ref>PMID:10739379</ref><ref>PMID:11248282</ref><ref>PMID:11728527</ref><ref>PMID:12945883</ref><ref>PMID:15650540</ref><ref>PMID:17393015</ref><ref>PMID:19135706</ref> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wu1|1wu1]], [[2j34|2j34]], [[2bq7|2bq7]], [[2y5g|2y5g]], [[2w3k|2w3k]], [[2vwo|2vwo]], [[1xka|1xka]], [[1nfw|1nfw]], [[2gd4|2gd4]], [[2vvv|2vvv]], [[2y5f|2y5f]], [[2xbx|2xbx]], [[1msx|1msx]], [[1lpg|1lpg]], [[2vvu|2vvu]], [[1p0s|1p0s]], [[2g00|2g00]], [[1mq6|1mq6]], [[1xkb|1xkb]], [[1iqe|1iqe]], [[1g2m|1g2m]], [[2vh0|2vh0]], [[1nfy|1nfy]], [[2uwl|2uwl]], [[2bok|2bok]], [[1hcg|1hcg]], [[1lpz|1lpz]], [[2w3i|2w3i]], [[2jkh|2jkh]], [[1z6e|1z6e]], [[2uwp|2uwp]], [[2xc4|2xc4]], [[2y81|2y81]], [[1g2l|1g2l]], [[1nfu|1nfu]], [[2xc0|2xc0]], [[2bq6|2bq6]], [[1fax|1fax]], [[1iqf|1iqf]], [[2y7x|2y7x]], [[1nl8|1nl8]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1lqd|1lqd]], [[2uwo|2uwo]], [[1c5m|1c5m]], [[1ioe|1ioe]], [[1f0s|1f0s]], [[1f0r|1f0r]], [[2xby|2xby]], [[2xc5|2xc5]], [[2y7z|2y7z]], [[1mq5|1mq5]], [[2bmg|2bmg]], [[1iqn|1iqn]], [[2xbv|2xbv]], [[2bqw|2bqw]], [[1iqm|1iqm]], [[1ezq|1ezq]], [[2vwl|2vwl]], [[2vh6|2vh6]], [[1fjs|1fjs]], [[1lpk|1lpk]], [[2j4i|2j4i]], [[2y5h|2y5h]], [[1nfx|1nfx]], [[2vwn|2vwn]], [[1iqj|1iqj]], [[2j94|2j94]], [[2j95|2j95]], [[2cji|2cji]], [[2boh|2boh]], [[2j38|2j38]], [[2vvc|2vvc]], [[2w26|2w26]], [[1iqi|1iqi]], [[2vwm|2vwm]], [[1kye|1kye]], [[2y82|2y82]], [[2y80|2y80]], [[1iqk|1iqk]], [[2wyj|2wyj]], [[1v3x|1v3x]], [[2fzz|2fzz]], [[2j2u|2j2u]], [[2xbw|2xbw]], [[2wyg|2wyg]], [[1ksn|1ksn]], [[1iql|1iql]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a7i RCSB], [http://www.ebi.ac.uk/pdbsum/4a7i PDBsum]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://omim.org/entry/227600 227600]]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
More than just the sum of its parts: The superadditivity effect of fragment linking on DeltaG was quantified by deconstructing two fXa inhibitors with congeneric fragments, but different linkers. By connecting both fragments with a single bond, a high linker contribution DeltaG(link) of -14.0 kJ mol(-1) results, which corresponds to an improvement in affinity by around 2.5 orders of magnitude relative to the sum of fragment DeltaG values. | |||
Fragment deconstruction of small, potent factor xa inhibitors: exploring the superadditivity energetics of fragment linking in protein-ligand complexes.,Nazare M, Matter H, Will DW, Wagner M, Urmann M, Czech J, Schreuder H, Bauer A, Ritter K, Wehner V Angew Chem Int Ed Engl. 2012 Jan 23;51(4):905-11. doi:, 10.1002/anie.201107091. Epub 2011 Dec 21. PMID:22190348<ref>PMID:22190348</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Factor Xa|Factor Xa]] | *[[Factor Xa|Factor Xa]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Coagulation factor Xa]] | [[Category: Coagulation factor Xa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Bauer, A | [[Category: Bauer, A]] | ||
[[Category: Czech, J | [[Category: Czech, J]] | ||
[[Category: Matter, H | [[Category: Matter, H]] | ||
[[Category: Nazare, M | [[Category: Nazare, M]] | ||
[[Category: Ritter, K | [[Category: Ritter, K]] | ||
[[Category: Schreuder, H | [[Category: Schreuder, H]] | ||
[[Category: Urmann, M | [[Category: Urmann, M]] | ||
[[Category: Wagner, M | [[Category: Wagner, M]] | ||
[[Category: Wehner, V | [[Category: Wehner, V]] | ||
[[Category: Will, D W | [[Category: Will, D W]] | ||
[[Category: Blood coagulation factor]] | [[Category: Blood coagulation factor]] | ||
[[Category: Calcium- binding]] | [[Category: Calcium- binding]] | ||
