4zfo: Difference between revisions
New page: '''Unreleased structure''' The entry 4zfo is ON HOLD Authors: Marino, S.F., Daumke, O., Olal, D. Description: J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269) [[Categ... |
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The | ==J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269)== | ||
<StructureSection load='4zfo' size='340' side='right'caption='[[4zfo]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zfo]] is a 6 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=4ZFO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZFO 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]] 1.895Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</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=4zfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zfo OCA], [https://pdbe.org/4zfo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zfo RCSB], [https://www.ebi.ac.uk/pdbsum/4zfo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zfo ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Note=A chromosomal aberration involving TNFRSF17 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with IL2. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.<ref>PMID:10903733</ref> <ref>PMID:10801128</ref> <ref>PMID:10973284</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Multiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a median life expectancy of less than seven years. Antibody-based therapies have demonstrated substantial clinical benefit for patients with hematological malignancies, particular in B cell Non-Hodgkin's lymphoma. The lack of immunotherapies specifically targeting MM cells led us to develop a human-mouse chimeric antibody directed against the B cell maturation antigen (BCMA), which is almost exclusively expressed on plasma cells and multiple myeloma cells. The high affinity antibody blocks the binding of the native ligands APRIL and BAFF to BCMA. This finding is rationalized by the high resolution crystal structure of the Fab fragment in complex with the extracellular domain of BCMA. Most importantly, the antibody effectively depletes MM cells in vitro and in vivo and substantially prolongs tumor-free survival under therapeutic conditions in a xenograft mouse model. A BCMA-antibody-based therapy is therefore a promising option for the effective treatment of multiple myeloma and autoimmune diseases. | |||
Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.,Oden F, Marino SF, Brand J, Scheu S, Kriegel C, Olal D, Takvorian A, Westermann J, Yilmaz B, Hinz M, Daumke O, Hopken UE, Muller G, Lipp M Mol Oncol. 2015 Mar 31. pii: S1574-7891(15)00068-X. doi:, 10.1016/j.molonc.2015.03.010. PMID:25953704<ref>PMID:25953704</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4zfo" style="background-color:#fffaf0;"></div> | ||
[[Category: Marino | |||
[[Category: | ==See Also== | ||
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Daumke O]] | |||
[[Category: Marino SF]] | |||
[[Category: Olal D]] |
Latest revision as of 13:59, 10 January 2024
J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269)J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269)
Structural highlights
DiseaseTNR17_HUMAN Note=A chromosomal aberration involving TNFRSF17 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with IL2. FunctionTNR17_HUMAN Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.[1] [2] [3] Publication Abstract from PubMedMultiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a median life expectancy of less than seven years. Antibody-based therapies have demonstrated substantial clinical benefit for patients with hematological malignancies, particular in B cell Non-Hodgkin's lymphoma. The lack of immunotherapies specifically targeting MM cells led us to develop a human-mouse chimeric antibody directed against the B cell maturation antigen (BCMA), which is almost exclusively expressed on plasma cells and multiple myeloma cells. The high affinity antibody blocks the binding of the native ligands APRIL and BAFF to BCMA. This finding is rationalized by the high resolution crystal structure of the Fab fragment in complex with the extracellular domain of BCMA. Most importantly, the antibody effectively depletes MM cells in vitro and in vivo and substantially prolongs tumor-free survival under therapeutic conditions in a xenograft mouse model. A BCMA-antibody-based therapy is therefore a promising option for the effective treatment of multiple myeloma and autoimmune diseases. Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.,Oden F, Marino SF, Brand J, Scheu S, Kriegel C, Olal D, Takvorian A, Westermann J, Yilmaz B, Hinz M, Daumke O, Hopken UE, Muller G, Lipp M Mol Oncol. 2015 Mar 31. pii: S1574-7891(15)00068-X. doi:, 10.1016/j.molonc.2015.03.010. PMID:25953704[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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