5ea0: Difference between revisions

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'''Unreleased structure'''


The entry 5ea0 is ON HOLD  until Paper Publication
==Structure of the antibody 7968 with human complement factor H-derived peptide==
<StructureSection load='5ea0' size='340' side='right' caption='[[5ea0]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ea0]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EA0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EA0 FirstGlance]. <br>
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ea0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ea0 OCA], [http://pdbe.org/5ea0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ea0 RCSB], [http://www.ebi.ac.uk/pdbsum/5ea0 PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/FHR2_HUMAN FHR2_HUMAN]] Might be involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.


Authors:  
A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.,Bushey RT, Moody MA, Nicely NL, Haynes BF, Alam SM, Keir ST, Bentley RC, Roy Choudhury K, Gottlin EB, Campa MJ, Liao HX, Patz EF Jr Cell Rep. 2016 May 17;15(7):1505-13. doi: 10.1016/j.celrep.2016.04.038. Epub 2016, May 5. PMID:27160908<ref>PMID:27160908</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 5ea0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alam, S M]]
[[Category: Bushey, R T]]
[[Category: Campa, M J]]
[[Category: Gottlin, E B]]
[[Category: Haynes, B F]]
[[Category: Liao, H X]]
[[Category: Moody, M A]]
[[Category: Nicely, N I]]
[[Category: Patz, E F]]
[[Category: Winkler, M T]]
[[Category: Complement factor h cfh scr19 scr19-20]]
[[Category: Immune system]]

Revision as of 10:58, 1 June 2016

Structure of the antibody 7968 with human complement factor H-derived peptideStructure of the antibody 7968 with human complement factor H-derived peptide

Structural highlights

5ea0 is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[FHR2_HUMAN] Might be involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism.

Publication Abstract from PubMed

Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.,Bushey RT, Moody MA, Nicely NL, Haynes BF, Alam SM, Keir ST, Bentley RC, Roy Choudhury K, Gottlin EB, Campa MJ, Liao HX, Patz EF Jr Cell Rep. 2016 May 17;15(7):1505-13. doi: 10.1016/j.celrep.2016.04.038. Epub 2016, May 5. PMID:27160908[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Bushey RT, Moody MA, Nicely NL, Haynes BF, Alam SM, Keir ST, Bentley RC, Roy Choudhury K, Gottlin EB, Campa MJ, Liao HX, Patz EF Jr. A Therapeutic Antibody for Cancer, Derived from Single Human B Cells. Cell Rep. 2016 May 17;15(7):1505-13. doi: 10.1016/j.celrep.2016.04.038. Epub 2016, May 5. PMID:27160908 doi:http://dx.doi.org/10.1016/j.celrep.2016.04.038

5ea0, resolution 2.00Å

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OCA