View source for 4a7i


==Factor Xa in complex with a potent 2-amino-ethane sulfonamide inhibitor==
<StructureSection load='4a7i' size='340' side='right'caption='[[4a7i]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4a7i]] is a 2 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=4A7I FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7i OCA], [https://pdbe.org/4a7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a7i RCSB], [https://www.ebi.ac.uk/pdbsum/4a7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7i ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://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 ==
[https://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4a7i" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor Xa|Factor Xa]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bauer A]]
[[Category: Czech J]]
[[Category: Matter H]]
[[Category: Nazare M]]
[[Category: Ritter K]]
[[Category: Schreuder H]]
[[Category: Urmann M]]
[[Category: Wagner M]]
[[Category: Wehner V]]
[[Category: Will DW]]