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1d5b

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(New page: 200px<br /> <applet load="1d5b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d5b, resolution 2.80&Aring;" /> '''UNLIGANDED MATURE O...)
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[[Image:1d5b.gif|left|200px]]<br />
 
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<applet load="1d5b" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1d5b, resolution 2.80&Aring;" />
 
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'''UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY'''<br />
 
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==Overview==
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==UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY==
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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.
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<StructureSection load='1d5b' size='340' side='right'caption='[[1d5b]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1d5b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1D5B FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1d5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d5b OCA], [https://pdbe.org/1d5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1d5b RCSB], [https://www.ebi.ac.uk/pdbsum/1d5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1d5b ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d5/1d5b_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1d5b ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known disease associated with this structure: Kappa light chain deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147200 147200]]
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1D5B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus_and_homo_sapiens Mus musculus and homo sapiens] with CD as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D5B OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Homo sapiens]]
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10651626 10651626]
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[[Category: Large Structures]]
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[[Category: Mus musculus and homo sapiens]]
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[[Category: Mus musculus]]
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[[Category: Protein complex]]
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[[Category: Hanson MA]]
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[[Category: Hanson, M.A.]]
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[[Category: Mundorff EC]]
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[[Category: Mundorff, E.C.]]
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[[Category: Schultz PG]]
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[[Category: Schultz, P.G.]]
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[[Category: Stevens RC]]
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[[Category: Stevens, R.C.]]
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[[Category: CD]]
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[[Category: immune system]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:29:01 2007''
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Current revision

UNLIGANDED MATURE OXY-COPE CATALYTIC ANTIBODY

PDB ID 1d5b

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