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< | ==48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID== | ||
<StructureSection load='1gaf' size='340' side='right'caption='[[1gaf]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1gaf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GAF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NPE:5-(PARA-NITROPHENYL+PHOSPHONATE)-PENTANOIC+ACID'>NPE</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gaf OCA], [https://pdbe.org/1gaf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gaf RCSB], [https://www.ebi.ac.uk/pdbsum/1gaf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gaf ProSAT]</span></td></tr> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ga/1gaf_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<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/main_output.php?pdb_ID=1gaf ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody. | |||
The immunological evolution of catalysis.,Patten PA, Gray NS, Yang PL, Marks CB, Wedemayer GJ, Boniface JJ, Stevens RC, Schultz PG Science. 1996 Feb 23;271(5252):1086-91. PMID:8599084<ref>PMID:8599084</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1gaf" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | |||
== | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Patten | [[Category: Patten PA]] | ||
[[Category: Schultz | [[Category: Schultz PG]] | ||
[[Category: Stevens | [[Category: Stevens RC]] | ||
[[Category: Wedemayer | [[Category: Wedemayer GJ]] | ||
Latest revision as of 03:00, 21 November 2024
48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID
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 germline genes used by the mouse to generate the esterolytic antibody 48G7 were cloned and expressed in an effort to increase our understanding of the detailed molecular mechanisms by which the immune system evolves catalytic function. The nine replacement mutations that were fixed during affinity maturation increased affinity for the transition state analogue by a factor of 10(4), primarily the result of a decrease in the dissociation rate of the hapten-antibody complex. There was a corresponding increase in the rate of reaction of antibody with substrate, k(cat)/k(m), from 1.7 x 10(2)M(-1) min(-1) to 1.4 x 10(4)M(-1) min(-1). The three-dimensional crystal structure of the 48G7-transition state analogue complex at 2.0 angstroms resolution indicates that one of the nine residues in which somatic mutations have been fixed directly contact the hapten. Thus, in the case of 48G7, affinity maturation appears to play a conformational role, either in reorganizing the active site geometry of limiting side-chain and backbone flexibility of the germline antibody. The crystal structure and analysis of somatic and directed active site mutants underscore the role of transition state stabilization in the evolution of this catalytic antibody. The immunological evolution of catalysis.,Patten PA, Gray NS, Yang PL, Marks CB, Wedemayer GJ, Boniface JJ, Stevens RC, Schultz PG Science. 1996 Feb 23;271(5252):1086-91. PMID:8599084[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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