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[[Image:2j4i.jpg|left|200px]]<br /><applet load="2j4i" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2j4i, resolution 1.8&Aring;" />
'''CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX'''<br />


==Overview==
==CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX==
<StructureSection load='2j4i' size='340' side='right'caption='[[2j4i]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2j4i]] 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=2J4I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J4I 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GSJ:1-PYRROLIDINEACETAMIDE,+3-[[(6-CHLORO-2-NAPHTHALENYL)SULFONYL]AMINO]-ALPHA-METHYL-N-(1-METHYLETHYL)-N-[2-[(METHYLSULFONYL)AMINO]ETHYL]-2-OXO-,+(ALPHAS,3S)-'>GSJ</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=2j4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j4i OCA], [https://pdbe.org/2j4i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j4i RCSB], [https://www.ebi.ac.uk/pdbsum/2j4i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j4i 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j4/2j4i_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j4i ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.
Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.


==Disease==
Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs.,Young RJ, Campbell M, Borthwick AD, Brown D, Burns-Kurtis CL, Chan C, Convery MA, Crowe MC, Dayal S, Diallo H, Kelly HA, King NP, Kleanthous S, Mason AM, Mordaunt JE, Patel C, Pateman AJ, Senger S, Shah GP, Smith PW, Watson NS, Weston HE, Zhou P Bioorg Med Chem Lett. 2006 Dec 1;16(23):5953-7. Epub 2006 Sep 18. PMID:16982190<ref>PMID:16982190</ref>
Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2J4I is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GSJ:'>GSJ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J4I OCA].
</div>
<div class="pdbe-citations 2j4i" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs., Young RJ, Campbell M, Borthwick AD, Brown D, Burns-Kurtis CL, Chan C, Convery MA, Crowe MC, Dayal S, Diallo H, Kelly HA, King NP, Kleanthous S, Mason AM, Mordaunt JE, Patel C, Pateman AJ, Senger S, Shah GP, Smith PW, Watson NS, Weston HE, Zhou P, Bioorg Med Chem Lett. 2006 Dec 1;16(23):5953-7. Epub 2006 Sep 18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16982190 16982190]
*[[Factor Xa|Factor Xa]]
[[Category: Coagulation factor Xa]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Borthwick, A D.]]
[[Category: Borthwick AD]]
[[Category: Brown, D.]]
[[Category: Brown D]]
[[Category: Campbell, M.]]
[[Category: Campbell M]]
[[Category: Chan, C.]]
[[Category: Chan C]]
[[Category: Convery, M A.]]
[[Category: Convery MA]]
[[Category: Crowe, M C.]]
[[Category: Crowe MC]]
[[Category: Dayal, S.]]
[[Category: Dayal S]]
[[Category: Diallo, H.]]
[[Category: Diallo H]]
[[Category: Kelly, H A.]]
[[Category: Kelly HA]]
[[Category: King, N Paul.]]
[[Category: Kleanthous S]]
[[Category: Kleanthous, S.]]
[[Category: Kurtis CL]]
[[Category: Kurtis, C L.]]
[[Category: Mason AM]]
[[Category: Mason, A M.]]
[[Category: Mordaunt JE]]
[[Category: Mordaunt, J E.]]
[[Category: Patel C]]
[[Category: Patel, C.]]
[[Category: Pateman AJ]]
[[Category: Pateman, A J.]]
[[Category: Paul King N]]
[[Category: Senger, S.]]
[[Category: Senger S]]
[[Category: Shah, G P.]]
[[Category: Shah GP]]
[[Category: Smith, P W.]]
[[Category: Smith PW]]
[[Category: Watson, N S.]]
[[Category: Watson NS]]
[[Category: Weston, H E.]]
[[Category: Weston HE]]
[[Category: Young, R J.]]
[[Category: Young RJ]]
[[Category: Zhou, P.]]
[[Category: Zhou P]]
[[Category: CA]]
[[Category: GSJ]]
[[Category: blood coagulation]]
[[Category: calcium]]
[[Category: complex]]
[[Category: egf-like domain]]
[[Category: gamma-carboxyglutamic acid]]
[[Category: glycoprotein]]
[[Category: hydrolase]]
[[Category: hydroxylation]]
[[Category: polymorphism]]
[[Category: protease]]
[[Category: serine protease]]
[[Category: zymogen]]
 
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