4lld

From Proteopedia

(Difference between revisions)

Revision as of 15:12, 5 August 2016

Structure of wild-type IgG1 antibody heavy chain constant domain 1 and light chain lambda constant domain (IgG1 CH1:Clambda) at 1.19A

Structural highlights

4lld is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4llm, 4llq, 4llu, 4llw, 4lly
Gene:	IGHG1 (HUMAN), IGLC2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM: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.

Publication Abstract from PubMed

Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.

Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.,Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, Hansen-Estruch C, Chamberlain AK, Truhlar SM, Conner EM, Atwell S, Kuhlman B, Demarest SJ Nat Biotechnol. 2014 Feb;32(2):191-8. doi: 10.1038/nbt.2797. Epub 2014 Jan 26. PMID:24463572^[1]

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

References

↑ Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, Hansen-Estruch C, Chamberlain AK, Truhlar SM, Conner EM, Atwell S, Kuhlman B, Demarest SJ. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol. 2014 Feb;32(2):191-8. doi: 10.1038/nbt.2797. Epub 2014 Jan 26. PMID:24463572 doi:http://dx.doi.org/10.1038/nbt.2797

1 Structural highlights
2 Disease
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lld"

@@ Line 1: / Line 1: @@
 ==Structure of wild-type IgG1 antibody heavy chain constant domain 1 and light chain lambda constant domain (IgG1 CH1:Clambda) at 1.19A==
 <StructureSection load='4lld' size='340' side='right' caption='[[4lld]], [[Resolution|resolution]] 1.19&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4llm|4llm]], [[4llq|4llq]], [[4llu|4llu]], [[4llw|4llw]], [[4lly|4lly]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGLC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4lld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lld OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4lld RCSB], [http://www.ebi.ac.uk/pdbsum/4lld PDBsum]</span></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=4lld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lld OCA], [http://pdbe.org/4lld PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lld RCSB], [http://www.ebi.ac.uk/pdbsum/4lld PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lld ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4lld" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4lld

From Proteopedia

Revision as of 15:12, 5 August 2016

Structure of wild-type IgG1 antibody heavy chain constant domain 1 and light chain lambda constant domain (IgG1 CH1:Clambda) at 1.19A

Structural highlights

Disease

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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