View source for 2vh6


==Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs==
<StructureSection load='2vh6' size='340' side='right'caption='[[2vh6]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vh6]] 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=2VH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VH6 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSV:2-(5-CHLOROTHIOPHEN-2-YL)-N-{(3S)-1-[3-FLUORO-2-(METHYLSULFONYL)BIPHENYL-4-YL]-2-OXOPYRROLIDIN-3-YL}ETHANESULFONAMIDE'>GSV</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=2vh6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vh6 OCA], [https://pdbe.org/2vh6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vh6 RCSB], [https://www.ebi.ac.uk/pdbsum/2vh6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vh6 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 ==
Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.

Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with biaryl P4 motifs.,Young RJ, Borthwick AD, Brown D, Burns-Kurtis CL, Campbell M, Chan C, Charbaut M, Chung CW, Convery MA, Kelly HA, Paul King N, Kleanthous S, Mason AM, Pateman AJ, Patikis AN, Pinto IL, Pollard DR, Senger S, Shah GP, Toomey JR, Watson NS, Weston HE Bioorg Med Chem Lett. 2008 Jan 1;18(1):23-7. Epub 2007 Nov 17. PMID:18054228<ref>PMID:18054228</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vh6" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor Xa|Factor Xa]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Borthwick AD]]
[[Category: Brown D]]
[[Category: Burns-Kurtis CL]]
[[Category: Campbell M]]
[[Category: Chan C]]
[[Category: Charbaut M]]
[[Category: Chung CW]]
[[Category: Convery MA]]
[[Category: Kelly HA]]
[[Category: King NP]]
[[Category: Kleanthous S]]
[[Category: Mason AM]]
[[Category: Pateman AJ]]
[[Category: Patikis AN]]
[[Category: Pinto IL]]
[[Category: Pollard DR]]
[[Category: Senger S]]
[[Category: Shah GP]]
[[Category: Toomey JR]]
[[Category: Watson NS]]
[[Category: Weston HE]]
[[Category: Young RJ]]