2y5h: Difference between revisions
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==FACTOR XA - CATION INHIBITOR COMPLEX== | |||
=== | <StructureSection load='2y5h' size='340' side='right' caption='[[2y5h]], [[Resolution|resolution]] 1.33Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2y5h]] 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=2Y5H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y5H FirstGlance]. <br> | |||
==Disease== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y5H:3-[(3AS,4R,5S,8AS,8BR)-4-[2-(5-CHLOROTHIOPHEN-2-YL)-1,3-OXAZOL-4-YL]-1,3-DIOXO-4,6,7,8,8A,8B-HEXAHYDRO-3AH-PYRROLO[3,4-A]PYRROLIZIN-2-YL]PROPYL-TRIMETHYL-AZANIUM'>Y5H</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]], [[2w3k|2w3k]], [[2vwo|2vwo]], [[1xka|1xka]], [[1nfw|1nfw]], [[2gd4|2gd4]], [[2vvv|2vvv]], [[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]], [[1g2l|1g2l]], [[1nfu|1nfu]], [[2xc0|2xc0]], [[1fax|1fax]], [[2bq6|2bq6]], [[1iqf|1iqf]], [[1nl8|1nl8]], [[1iqg|1iqg]], [[1iqh|1iqh]], [[1lqd|1lqd]], [[2uwo|2uwo]], [[1c5m|1c5m]], [[1ioe|1ioe]], [[1f0s|1f0s]], [[1f0r|1f0r]], [[2xby|2xby]], [[2xc5|2xc5]], [[1mq5|1mq5]], [[2bmg|2bmg]], [[1iqn|1iqn]], [[2xbv|2xbv]], [[2bqw|2bqw]], [[1iqm|1iqm]], [[1ezq|1ezq]], [[2vwl|2vwl]], [[2vh6|2vh6]], [[1fjs|1fjs]], [[1lpk|1lpk]], [[2j4i|2j4i]], [[1nfx|1nfx]], [[2vwn|2vwn]], [[2j94|2j94]], [[1iqj|1iqj]], [[2cji|2cji]], [[2j95|2j95]], [[2boh|2boh]], [[2j38|2j38]], [[2w26|2w26]], [[2vvc|2vvc]], [[1iqi|1iqi]], [[2vwm|2vwm]], [[1kye|1kye]], [[1iqk|1iqk]], [[2wyj|2wyj]], [[1v3x|1v3x]], [[2fzz|2fzz]], [[2j2u|2j2u]], [[2xbw|2xbw]], [[1ksn|1ksn]], [[1iql|1iql]], [[2wyg|2wyg]], [[2y5g|2y5g]], [[2y5f|2y5f]]</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=2y5h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y5h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y5h RCSB], [http://www.ebi.ac.uk/pdbsum/2y5h 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 == | |||
Factor Xa, a serine protease from the blood coagulation cascade, is an ideal enzyme for molecular recognition studies, as its active site is highly shape-persistent and features distinct, concave sub-pockets. We developed a family of non-peptidic, small-molecule inhibitors with a central tricyclic core orienting a neutral heterocyclic substituent into the S1 pocket and a quaternary ammonium ion into the aromatic box in the S4 pocket. The substituents were systematically varied to investigate cation-pi interactions in the S4 pocket, optimal heterocyclic stacking on the flat peptide walls lining the S1 pocket, and potential water replacements in both the S1 and the S4 pockets. Structure-activity relationships were established to reveal and quantify contributions to the binding free enthalpy, resulting from single-atom replacements or positional changes in the ligands. A series of high-affinity ligands with inhibitory constants down to K(i) =2 nM were obtained and their proposed binding geometries confirmed by X-ray co-crystal structures of protein-ligand complexes. | |||
Molecular Recognition at the Active Site of Factor Xa: Cation-pi Interactions, Stacking on Planar Peptide Surfaces, and Replacement of Structural Water.,Salonen LM, Holland MC, Kaib PS, Haap W, Benz J, Mary JL, Kuster O, Schweizer WB, Banner DW, Diederich F Chemistry. 2011 Dec 9. doi: 10.1002/chem.201102571. PMID:22162109<ref>PMID:22162109</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: Banner, D W | [[Category: Banner, D W]] | ||
[[Category: Benz, J | [[Category: Benz, J]] | ||
[[Category: Diederich, F | [[Category: Diederich, F]] | ||
[[Category: Haap, W | [[Category: Haap, W]] | ||
[[Category: Holland, M C | [[Category: Holland, M C]] | ||
[[Category: Salonen, L M | [[Category: Salonen, L M]] | ||
[[Category: Blood clotting]] | [[Category: Blood clotting]] | ||
[[Category: Blood coagulation]] | [[Category: Blood coagulation]] | ||