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3fjt

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Revision as of 06:43, 1 November 2017

Crystal structure of a human Fc fragment engineered for extended serum half-life

Structural highlights

3fjt 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.
Ligands:	, , ,
Gene:	IgG1, IGHG1 (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.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The first three-dimensional structure of a human Fc fragment genetically engineered for improved pharmacokinetics properties is reported. When introduced into the C(H)2 domain of human immunoglobulin G (IgG) molecules, the triple mutation M252Y/S254T/T256E ('YTE') causes an about 10-fold increase in their binding to the human neonatal Fc receptor (FcRn). This translates into an almost 4-fold increase in the serum half-life of YTE-containing human IgGs in cynomolgus monkeys. A recombinantly produced human Fc/YTE fragment was crystallized and its structure solved at a resolution of 2.5A using molecular replacement. This revealed that Fc/YTE three-dimensional structure is very similar to that of other human Fc fragments in the experimentally visible region spanning residues 236-444. We propose that the enhanced interaction between Fc/YTE and human FcRn is likely mediated by local effects at the substitutions sites. Molecular modeling suggested that potential favorable hydrogen bonds along with an increase in the surface of contact between the two partners may account in part for the corresponding increase in affinity.

Structural characterization of a human Fc fragment engineered for extended serum half-life.,Oganesyan V, Damschroder MM, Woods RM, Cook KE, Wu H, Dall'acqua WF Mol Immunol. 2009 May;46(8-9):1750-5. Epub 2009 Feb 27. PMID:19250681^[1]

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

References

↑ Oganesyan V, Damschroder MM, Woods RM, Cook KE, Wu H, Dall'acqua WF. Structural characterization of a human Fc fragment engineered for extended serum half-life. Mol Immunol. 2009 May;46(8-9):1750-5. Epub 2009 Feb 27. PMID:19250681 doi:10.1016/j.molimm.2009.01.026

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3fjt"

@@ Line 1: / Line 1: @@
 ==Crystal structure of a human Fc fragment engineered for extended serum half-life==
 <StructureSection load='3fjt' size='340' side='right' caption='[[3fjt]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IgG1, IGHG1 ([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=3fjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjt OCA], [http://pdbe.org/3fjt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fjt RCSB], [http://www.ebi.ac.uk/pdbsum/3fjt 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=3fjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fjt OCA], [http://pdbe.org/3fjt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fjt RCSB], [http://www.ebi.ac.uk/pdbsum/3fjt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fjt ProSAT]</span></td></tr>
 </table>
 == Disease ==

3fjt

From Proteopedia

Revision as of 06:43, 1 November 2017

Crystal structure of a human Fc fragment engineered for extended serum half-life

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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