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1gaf

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{{STRUCTURE_1gaf| PDB=1gaf | SCENE= }}
{{STRUCTURE_1gaf| PDB=1gaf | SCENE= }}
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'''48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID'''
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===48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 8599084 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8599084}}
==About this Structure==
==About this Structure==
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[[Category: Esterolytic]]
[[Category: Esterolytic]]
[[Category: Fab]]
[[Category: Fab]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:20:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 04:59:29 2008''

Revision as of 01:59, 1 July 2008

Image:1gaf.png

Template:STRUCTURE 1gaf

48G7 HYBRIDOMA LINE FAB COMPLEXED WITH HAPTEN 5-(PARA-NITROPHENYL PHOSPHONATE)-PENTANOIC ACID

Template:ABSTRACT PUBMED 8599084

About this Structure

1GAF is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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