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Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task

Academic Article
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Overview

related to degree

  • Larsen, Nicholas, Ph.D. in Biology, Scripps Research 1998 - 2002

authors

  • Karlstrom, A.
  • Zhong, Guo-Fu
  • Rader, Christoph
  • Larsen, Nicholas
  • Heine, A.
  • Fuller, R.
  • List, B.
  • Tanaka, F.
  • Wilson, Ian
  • Barbas III, Carlos
  • Lerner, Richard

publication date

  • April 2000

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • Catalytic aldolase antibodies generated by immunization with two different, but structurally related, beta-diketone haptens were cloned and sequenced to study similarities and differences between independently evolved catalysts. Kinetic and sequence analysis coupled with mutagenesis, structural, and modeling studies reveal that the defining event in the evolution of these catalysts was a somatic mutation that placed a lysine residue in a deep, yet otherwise unrefined, hydrophobic pocket. We suggest that covalent chemistries may be as readily selected from the immune repertoire as the traditional noncovalent interactions that have formed the basis of immunochemistry until this time. Further, we believe that these experiments recapitulate the defining events in the evolution of nature's enzymes, particularly as they relate to chemical mechanism, catalytic promiscuity, and gene duplication.

subject areas

  • Amino Acid Sequence
  • Animals
  • Antibodies, Catalytic
  • Binding Sites
  • Cell Line
  • Cloning, Molecular
  • Evolution, Molecular
  • Fructose-Bisphosphate Aldolase
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation
  • Sequence Homology, Amino Acid
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Identity

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.97.8.3878

PubMed ID

  • 10760259
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Additional Document Info

start page

  • 3878

end page

  • 3883

volume

  • 97

issue

  • 8

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