1pg7

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{{STRUCTURE_1pg7| PDB=1pg7 | SCENE= }}
 
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===Murine 6A6 Fab in complex with humanized anti-Tissue Factor D3H44 Fab===
 
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{{ABSTRACT_PUBMED_12888350}}
 
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==About this Structure==
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==Murine 6A6 Fab in complex with humanized anti-Tissue Factor D3H44 Fab==
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[[1pg7]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PG7 OCA].
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<StructureSection load='1pg7' size='340' side='right'caption='[[1pg7]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pg7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PG7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PG7 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]] 2.5&#8491;</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=1pg7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pg7 OCA], [https://pdbe.org/1pg7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pg7 RCSB], [https://www.ebi.ac.uk/pdbsum/1pg7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pg7 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
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== Function ==
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[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
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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/pg/1pg7_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=1pg7 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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6A6 is a murine monoclonal antibody raised against the humanized anti-tissue factor antibody D3H44. 6A6 is able to completely neutralize the anticoagulant activity of D3H44 in tissue factor-dependent functional assays, such as endotoxin-induced whole blood clotting, prothrombin time, as well as factor X and factor IX activation. ELISA-type assays further showed that 6A6 binds to an epitope with critical determinants on the V(L) domain of D3H44. The possibility that the anti-idiotypic 6A6 might carry an "internal image" of the original antigen (tissue factor) was examined using the X-ray structure of the 6A6-Fab/D3H44-Fab complex determined at 2.5A resolution. We find that 6A6 structurally mimics tissue factor only so far as it combines with the antigen recognition surface of D3H44. While 6A6 contacts both V(L) and V(H) domains of D3H44, as does tissue factor, there is more contact with the D3H44 V(L) domain and less with the D3H44 V(H) domain relative to the tissue factor contacts on D3H44. Additionally, there is an almost total lack of correspondence between 6A6 and tissue factor at the level of amino acid side-chain functional groups. Despite the fact that both tissue factor and 6A6 are composed largely of beta-sheets, they present fundamentally different elements of secondary structure to D3H44; tissue factor presents beta-sheets edge-on, while 6A6 uses mostly loops. Finally, the finding that 6A6 competes with tissue factor for D3H44 binding raises the possibility of using 6A6 as an antidote for D3H44 anticoagulant therapy. To this end, we constructed a chimeric murine/human 6A6-Fab, which effectively neutralized D3H44 and fully restored tissue factor function in enzymatic assays.
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==See Also==
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Structural insight into how an anti-idiotypic antibody against D3H44 (anti-tissue factor antibody) restores normal coagulation.,Eigenbrot C, Meng YG, Krishnamurthy R, Lipari MT, Presta L, Devaux B, Wong T, Moran P, Bullens S, Kirchhofer D J Mol Biol. 2003 Aug 8;331(2):433-46. PMID:12888350<ref>PMID:12888350</ref>
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*[[Antibody|Antibody]]
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:012888350</ref><references group="xtra"/><references/>
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</div>
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<div class="pdbe-citations 1pg7" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Synthetic construct sequences]]
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[[Category: Bullens S]]
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[[Category: Bullens, S.]]
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[[Category: Devaux B]]
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[[Category: Devaux, B.]]
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[[Category: Eigenbrot C]]
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[[Category: Eigenbrot, C.]]
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[[Category: Kirchhofer D]]
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[[Category: Kirchhofer, D.]]
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[[Category: Krishnamurthy R]]
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[[Category: Krishnamurthy, R.]]
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[[Category: Lipari MT]]
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[[Category: Lipari, M T.]]
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[[Category: Meng YG]]
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[[Category: Meng, Y G.]]
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[[Category: Moran P]]
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[[Category: Moran, P.]]
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[[Category: Presta L]]
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[[Category: Presta, L.]]
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[[Category: Wong T]]
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[[Category: Wong, T.]]
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[[Category: Immune system]]
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Current revision

Murine 6A6 Fab in complex with humanized anti-Tissue Factor D3H44 Fab

PDB ID 1pg7

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