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1fax

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[[Image:1fax.jpg|left|200px]]<br /><applet load="1fax" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fax, resolution 3.0&Aring;" />
 
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'''COAGULATION FACTOR XA INHIBITOR COMPLEX'''<br />
 
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==Overview==
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==COAGULATION FACTOR XA INHIBITOR COMPLEX==
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The 3.0-A resolution x-ray structure of human des-Gla-coagulation factor, Xa (fXa) has been determined in complex with the synthetic inhibitor, DX-9065a. The binding geometry is characterized primarily by two, interaction sites: the naphthamidine group is fixed in the S1 pocket by a, typical salt bridge to Asp-189, while the pyrrolidine ring binds in the, unique aryl-binding site (S4) of fXa. Unlike the large majority of, inhibitor complexes with serine proteinases, Gly-216 (S3) does not, contribute to hydrogen bond formation. In contrast to typical thrombin, binding modes, the S2 site of fXa cannot be used by DX-9065a since it is, blocked by Tyr-99, and the aryl-binding site (S4) of fXa is lined by, carbonyl oxygen atoms that can accommodate positive charges. This has, implications for natural substrate recognition as well as for drug design.
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<StructureSection load='1fax' size='340' side='right'caption='[[1fax]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fax]] 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=1FAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FAX FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<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=DX9:(2S)-3-(7-CARBAMIMIDOYLNAPHTHALEN-2-YL)-2-[4-({(3R)-1-[(1Z)-ETHANIMIDOYL]PYRROLIDIN-3-YL}OXY)PHENYL]PROPANOIC+ACID'>DX9</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fax OCA], [https://pdbe.org/1fax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fax RCSB], [https://www.ebi.ac.uk/pdbsum/1fax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fax ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fa/1fax_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1fax ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The 3.0-A resolution x-ray structure of human des-Gla-coagulation factor Xa (fXa) has been determined in complex with the synthetic inhibitor DX-9065a. The binding geometry is characterized primarily by two interaction sites: the naphthamidine group is fixed in the S1 pocket by a typical salt bridge to Asp-189, while the pyrrolidine ring binds in the unique aryl-binding site (S4) of fXa. Unlike the large majority of inhibitor complexes with serine proteinases, Gly-216 (S3) does not contribute to hydrogen bond formation. In contrast to typical thrombin binding modes, the S2 site of fXa cannot be used by DX-9065a since it is blocked by Tyr-99, and the aryl-binding site (S4) of fXa is lined by carbonyl oxygen atoms that can accommodate positive charges. This has implications for natural substrate recognition as well as for drug design.
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==Disease==
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X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition.,Brandstetter H, Kuhne A, Bode W, Huber R, von der Saal W, Wirthensohn K, Engh RA J Biol Chem. 1996 Nov 22;271(47):29988-92. PMID:8939944<ref>PMID:8939944</ref>
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Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1FAX 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=DX9:'>DX9</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=CAT:Catalytic+Center+Of+SER+Protease'>CAT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FAX OCA].
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</div>
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<div class="pdbe-citations 1fax" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition., Brandstetter H, Kuhne A, Bode W, Huber R, von der Saal W, Wirthensohn K, Engh RA, J Biol Chem. 1996 Nov 22;271(47):29988-92. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8939944 8939944]
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*[[Factor Xa|Factor Xa]]
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[[Category: Coagulation factor Xa]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Brandstetter, H.]]
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[[Category: Brandstetter H]]
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[[Category: Engh, R.A.]]
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[[Category: Engh RA]]
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[[Category: CA]]
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[[Category: DX9]]
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[[Category: blood coagulation factor]]
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[[Category: calcium-binding]]
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[[Category: gamma-carboxyglutamic acid]]
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[[Category: glycoprotein]]
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[[Category: hydrolase]]
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[[Category: plasma]]
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[[Category: serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:39:41 2008''
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Current revision

COAGULATION FACTOR XA INHIBITOR COMPLEX

PDB ID 1fax

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