25c8: Difference between revisions
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==CATALYTIC ANTIBODY 5C8, FAB-HAPTEN COMPLEX== | ==CATALYTIC ANTIBODY 5C8, FAB-HAPTEN COMPLEX== | ||
<StructureSection load='25c8' size='340' side='right' caption='[[25c8]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='25c8' size='340' side='right' caption='[[25c8]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
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<table><tr><td colspan='2'>[[25c8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=25C8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=25C8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[25c8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=25C8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=25C8 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GEP:N-METHYL-N-(PARA-GLUTARAMIDOPHENYL-ETHYL)-PIPERIDINIUM+ION'>GEP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GEP:N-METHYL-N-(PARA-GLUTARAMIDOPHENYL-ETHYL)-PIPERIDINIUM+ION'>GEP</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=25c8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=25c8 OCA], [http://pdbe.org/25c8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=25c8 RCSB], [http://www.ebi.ac.uk/pdbsum/25c8 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=25c8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=25c8 OCA], [http://pdbe.org/25c8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=25c8 RCSB], [http://www.ebi.ac.uk/pdbsum/25c8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=25c8 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/5c/25c8_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/5c/25c8_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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==See Also== | ==See Also== | ||
*[[Monoclonal | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:25, 9 May 2018
CATALYTIC ANTIBODY 5C8, FAB-HAPTEN COMPLEXCATALYTIC ANTIBODY 5C8, FAB-HAPTEN COMPLEX
Structural highlights
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 PubMedThe catalysis of disfavored chemical reactions, especially those with no known natural enzyme counterparts, is one of the most promising achievements of catalytic antibody research. Antibodies 5C8, 14B9, 17F6, and 26D9, elicited by two different transition-state analogues, catalyze disfavored endo-tet cyclization reactions of trans-epoxy alcohols, in formal violation of Baldwin's rules for ring closure. Thus far, neither chemical nor enzyme catalysis has been capable of emulating the extraordinary activity and specificity of these antibodies. X-ray structures of two complexes of Fab 5C8 with the original hapten and with an inhibitor have been determined to 2.0 A resolution. The Fab structure has an active site that contains a putative catalytic diad, consisting of AspH95 and HisL89, capable of general acid/base catalysis. The stabilization of a positive charge that develops along the reaction coordinate appears to be an important factor for rate enhancement and for directing the reaction along the otherwise disfavored pathway. Sequence analysis of the four catalytic antibodies, as well as four inactive antibodies that strongly bind the transition-state analogues, suggests a conserved catalytic mechanism. The occurrence of the putative base HisL89 in all active antibodies, its absence in three out of the four analyzed inactive antibodies, and the rarity of a histidine at this position in immunoglobulins support an important catalytic role for this residue. Structural basis for antibody catalysis of a disfavored ring closure reaction.,Gruber K, Zhou B, Houk KN, Lerner RA, Shevlin CG, Wilson IA Biochemistry. 1999 Jun 1;38(22):7062-74. PMID:10353817[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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