View source for 2y81


==Structure and property based design of factor Xa inhibitors: pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs==
<StructureSection load='2y81' size='340' side='right'caption='[[2y81]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2y81]] 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=2Y81 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y81 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=931:6-CHLORO-N-((3S)-2-OXO-1-{4-[(2R)-2--PYRROLIDINYL]+PHENYL}-3-PYRROLIDINYL)-2-NAPHTHALENESULFONAMIDE'>931</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=2y81 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y81 OCA], [https://pdbe.org/2y81 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y81 RCSB], [https://www.ebi.ac.uk/pdbsum/2y81 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y81 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 ==
The rational design, syntheses and evaluation of potent sulfonamidopyrrolidin-2-one-based factor Xa inhibitors incorporating aminoindane and phenylpyrrolidine P4 motifs are described. These series delivered highly potent anticoagulant compounds with excellent oral pharmacokinetic profiles; however, significant time dependant P450 inhibition was an issue for the aminoindane series, but this was not observed with the phenylpyrrolidine motif, which produced candidate quality molecules with potential for once-daily oral dosing in humans.

Structure and property based design of factor Xa inhibitors: Pyrrolidin-2-ones with aminoindane and phenylpyrrolidine P4 motifs.,Young RJ, Adams C, Blows M, Brown D, Burns-Kurtis CL, Chan C, Chaudry L, Convery MA, Davies DE, Exall AM, Foster G, Harling JD, Hortense E, Irvine S, Irving WR, Jackson S, Kleanthous S, Pateman AJ, Patikis AN, Roethka TJ, Senger S, Stelman GJ, Toomey JR, West RI, Whittaker C, Zhou P, Watson NS Bioorg Med Chem Lett. 2011 Mar 15;21(6):1582-7. Epub 2011 Feb 1. PMID:21349710<ref>PMID:21349710</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2y81" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor Xa|Factor Xa]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Adams C]]
[[Category: Blows M]]
[[Category: Brown D]]
[[Category: Burns-Kurtis CL]]
[[Category: Chan C]]
[[Category: Chaudry L]]
[[Category: Convery MA]]
[[Category: Davies DE]]
[[Category: Exall AM]]
[[Category: Foster G]]
[[Category: Harling JD]]
[[Category: Hortense E]]
[[Category: Irvine S]]
[[Category: Irving WR]]
[[Category: Jackson S]]
[[Category: Kleanthous S]]
[[Category: Pateman AJ]]
[[Category: Patikis AN]]
[[Category: Roethka TJ]]
[[Category: Senger S]]
[[Category: Stelman GJ]]
[[Category: Toomey JR]]
[[Category: Watson NS]]
[[Category: West RI]]
[[Category: Whittaker C]]
[[Category: Young RJ]]
[[Category: Zhou P]]