1nl0

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{{STRUCTURE_1nl0| PDB=1nl0 | SCENE= }}
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==Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12==
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===Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12===
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<StructureSection load='1nl0' size='340' side='right' caption='[[1nl0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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{{ABSTRACT_PUBMED_14722079}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nl0]] is a 3 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=1NL0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NL0 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">10C12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nl0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1nl0 RCSB], [http://www.ebi.ac.uk/pdbsum/1nl0 PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://omim.org/entry/306900 306900]]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref> Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide. Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
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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/nl/1nl0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata 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 binding of Factor IX to membranes during blood coagulation is mediated by the N-terminal gamma-carboxyglutamic acid-rich (Gla) domain, a membrane-anchoring domain found on vitamin K-dependent blood coagulation and regulatory proteins. Conformation-specific anti-Factor IX antibodies are directed at the calcium-stabilized Gla domain and interfere with Factor IX-membrane interaction. One such antibody, 10C12, recognizes the calcium-stabilized form of the Gla domain of Factor IX. We prepared the fully carboxylated Gla domain of Factor IX by solid phase peptide synthesis and crystallized Factor IX-(1-47) in complex with Fab fragments of the 10C12 antibody. The overall structure of the Gla domain in the Factor IX-(1-47)-antibody complex at 2.2 A is similar to the structure of the Factor IX Gla domain in the presence of calcium ions as determined by NMR spectroscopy (Freedman, S. J., Furie, B. C., Furie, B., and Baleja, J. D. (1995) Biochemistry 34, 12126-12137) and by x-ray crystallography (Shikamoto, Y., Morita, T., Fujimoto, Z., and Mizuno, H. (2003) J. Biol. Chem. 278, 24090-24094). The complex structure shows that the complementarity determining region loops of the 10C12 antibody form a hydrophobic pocket to accommodate the hydrophobic patch of the Gla domain consisting of Leu-6, Phe-9, and Val-10. Polar interactions also play an important role in the antibody-antigen recognition. Furthermore, the calcium coordination network of the Factor IX Gla domain is different than in Gla domain structures of other vitamin K-dependent proteins. We conclude that this antibody is directed at the membrane binding site in the omega loop of Factor IX and blocks Factor IX function by inhibiting its interaction with membranes.
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==Disease==
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Crystal structure of the calcium-stabilized human factor IX Gla domain bound to a conformation-specific anti-factor IX antibody.,Huang M, Furie BC, Furie B J Biol Chem. 2004 Apr 2;279(14):14338-46. Epub 2004 Jan 13. PMID:14722079<ref>PMID:14722079</ref>
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[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://omim.org/entry/306900 306900]]; also known as Christmas disease.<ref>PMID:8295821</ref><ref>PMID:2592373</ref><ref>PMID:2743975</ref><ref>PMID:6603618</ref><ref>PMID:3009023</ref><ref>PMID:3790720</ref><ref>PMID:3401602</ref><ref>PMID:3243764</ref><ref>PMID:2713493</ref><ref>PMID:2714791</ref><ref>PMID:2773937</ref><ref>PMID:2775660</ref><ref>PMID:2753873</ref><ref>PMID:2738071</ref><ref>PMID:2472424</ref><ref>PMID:2339358</ref><ref>PMID:2372509</ref><ref>PMID:2162822</ref><ref>PMID:1958666</ref><ref>PMID:1902289</ref><ref>PMID:1346975</ref><ref>PMID:1615485</ref><ref>PMID:8257988</ref><ref>PMID:8076946</ref><ref>PMID:8199596</ref><ref>PMID:7981722</ref><ref>PMID:8680410</ref><ref>PMID:9222764</ref><ref>PMID:9590153</ref><ref>PMID:9452115</ref><ref>PMID:9600455</ref><ref>PMID:10698280</ref><ref>PMID:10094553</ref><ref>PMID:11122099</ref><ref>PMID:12588353</ref><ref>PMID:12604421</ref> Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide. Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
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</div>
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==About this Structure==
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[[1nl0]] is a 3 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=1NL0 OCA].
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==See Also==
==See Also==
*[[Factor IX|Factor IX]]
*[[Factor IX|Factor IX]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:014722079</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Furie, B.]]
[[Category: Furie, B.]]

Revision as of 17:24, 29 September 2014

Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12

1nl0, resolution 2.20Å

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