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1i7z

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Revision as of 10:42, 27 September 2017

ANTIBODY GNC92H2 BOUND TO LIGAND

Structural highlights

1i7z is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.^[1] [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

Murine monoclonal antibody GNC92H2 was elicited by active immunization with a cocaine immunoconjugate and binds free cocaine with excellent specificity and moderate affinity. Improvement of affinity, as well as humanization of GNC92H2, would be advantageous in immunopharmacotherapy for cocaine addiction, and for emergency cases of drug overdose. Toward this end, the crystal structure of an engineered murine-human chimeric Fab of GNC92H2 complexed with cocaine was determined at 2.3 A resolution. Structural analysis reveals a binding pocket with high shape and charge complementarity to the cocaine framework, which explains the specificity for cocaine, as opposed to the pharmacologically inactive cocaine metabolites. Importantly, the structure provides a foundation for mutagenesis to enhance the binding affinity for cocaine and potent cocaine derivatives, such as cocaethylene, and for additional humanization of the antibody.

Crystal structure of a cocaine-binding antibody.,Larsen NA, Zhou B, Heine A, Wirsching P, Janda KD, Wilson IA J Mol Biol. 2001 Aug 3;311(1):9-15. PMID:11469854^[2]

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

References

↑ Stavnezer-Nordgren J, Kekish O, Zegers BJ. Molecular defects in a human immunoglobulin kappa chain deficiency. Science. 1985 Oct 25;230(4724):458-61. PMID:3931219
↑ Larsen NA, Zhou B, Heine A, Wirsching P, Janda KD, Wilson IA. Crystal structure of a cocaine-binding antibody. J Mol Biol. 2001 Aug 3;311(1):9-15. PMID:11469854 doi:10.1006/jmbi.2001.4839

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/1i7z"

@@ Line 1: / Line 1: @@
 ==ANTIBODY GNC92H2 BOUND TO LIGAND==
 <StructureSection load='1i7z' size='340' side='right' caption='[[1i7z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1i7z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I7Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I7Z FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1i7z]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I7Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I7Z FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COC:COCAINE'>COC</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=1i7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7z OCA], [http://pdbe.org/1i7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i7z RCSB], [http://www.ebi.ac.uk/pdbsum/1i7z 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=1i7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7z OCA], [http://pdbe.org/1i7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i7z RCSB], [http://www.ebi.ac.uk/pdbsum/1i7z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1i7z ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1i7z ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 31: / Line 32: @@
 __TOC__
 </StructureSection>
-[[Category: Lk3 transgenic mice]]
 [[Category: Larsen, N A]]
 [[Category: Wilson, I A]]

1i7z

From Proteopedia

Revision as of 10:42, 27 September 2017

ANTIBODY GNC92H2 BOUND TO LIGAND

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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