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1d6v

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Revision as of 02:02, 12 September 2015

CONFORMATION EFFECTS IN BIOLOGICAL CATALYSIS INTRODUCED BY OXY-COPE ANTIBODY MATURATION

Structural highlights

1d6v is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1axs, 1d5i, 1d5b
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

Antibody AZ-28 was generated against the chairlike transition-state analogue (TSA) 1 and catalyzes the oxy-Cope rearrangement of substrate 2 to product 3. The germline precursor to AZ-28 catalyzes the reaction with a 35-fold higher rate (k(cat)/k(uncat) = 163 000), despite a 40-fold lower binding affinity for TSA.1 (K(D) = 670 nM). To determine the structural basis for the differences in the binding and catalytic properties of the germline and affinity-matured antibodies, the X-ray crystal structures of the unliganded and TSA.1 complex of antibody AZ-28 have been determined at 2.8 and 2.6 A resolution, respectively; the structures of the unliganded and TSA.1 complex of the germline precursor to AZ-28 were both determined at 2. 0 A resolution. In the affinity-matured antibody.hapten complex the TSA is fixed in a catalytically unfavorable conformation by a combination of van der Waals and hydrogen-bonding interactions. The 2- and 5-phenyl substituents of TSA.1 are almost perpendicular to the cyclohexyl ring, leading to decreased orbital overlap and decreased stabilization of the putative transition state. The active site of the germline antibody appears to have an increased degree of flexibility-CDRH3 moves 4.9 A outward from the active site upon binding of TSA.1. We suggest that this conformational flexibility in the germline antibody, which results in a lower binding affinity for TSA.1, allows dynamic changes in the dihedral angle of the 2-phenyl substituent along the reaction coordinate. These conformational changes in turn lead to enhanced orbital overlap and increased catalytic rate. These studies suggest that protein and substrate dynamics play a key role in this antibody-catalyzed reaction.

Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement.,Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC Biochemistry. 2000 Feb 1;39(4):627-32. PMID:10651626^[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
↑ Mundorff EC, Hanson MA, Varvak A, Ulrich H, Schultz PG, Stevens RC. Conformational effects in biological catalysis: an antibody-catalyzed oxy-cope rearrangement. Biochemistry. 2000 Feb 1;39(4):627-32. PMID:10651626

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1d6v"

@@ Line 2: / Line 2: @@
 <StructureSection load='1d6v' size='340' side='right' caption='[[1d6v]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1d6v]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D6V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1D6V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1d6v]] is a 2 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=1D6V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1D6V FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=HOP:(1S,2S,5S)2-(4-GLUTARIDYLBENZYL)-5-PHENYL-1-CYCLOHEXANOL'>HOP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1axs|1axs]], [[1d5i|1d5i]], [[1d5b|1d5b]]</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=1d6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d6v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1d6v RCSB], [http://www.ebi.ac.uk/pdbsum/1d6v 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=1d6v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d6v OCA], [http://pdbe.org/1d6v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1d6v RCSB], [http://www.ebi.ac.uk/pdbsum/1d6v PDBsum]</span></td></tr>
 </table>
 == Disease ==
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1d6v" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Hanson, M A]]
 [[Category: Mundorff, E C]]

1d6v

From Proteopedia

Revision as of 02:02, 12 September 2015

CONFORMATION EFFECTS IN BIOLOGICAL CATALYSIS INTRODUCED BY OXY-COPE ANTIBODY MATURATION

Structural highlights

Disease

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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