1nl0

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[[Image:1nl0.jpg|left|200px]]<br /><applet load="1nl0" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1nl0.jpg|left|200px]]
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caption="1nl0, resolution 2.20&Aring;" />
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'''Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12'''<br />
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{{Structure
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|PDB= 1nl0 |SIZE=350|CAPTION= <scene name='initialview01'>1nl0</scene>, resolution 2.20&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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|ACTIVITY=
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|GENE= 10C12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal structure of human factor IX Gla domain in complex of an inhibitory antibody, 10C12'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1NL0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NL0 OCA].
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1NL0 is a [[Single protein]] structure of 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].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14722079 14722079]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/14722079 14722079]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: immune system]]
[[Category: immune system]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:07:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:58:13 2008''

Revision as of 10:58, 20 March 2008

Image:1nl0.jpg


PDB ID 1nl0

Drag the structure with the mouse to rotate
, resolution 2.20Å
Ligands: and
Gene: 10C12 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



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


Contents

Overview

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.

Disease

Known diseases associated with this structure: Hemophilia B OMIM:[306900], Warfarin sensitivity OMIM:[306900]

About this Structure

1NL0 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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