| Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task. | |
| | |
MedLine Citation:
|
PMID: 10760259 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
A Karlstrom; G Zhong; C Rader; N A Larsen; A Heine; R Fuller; B List; F Tanaka; I A Wilson; C F Barbas; R A Lerner |
Related Documents
:
|
14698659 - New insights into the evolutionary relationships between arenaviruses provided by compa... 11163959 - The compositional evolution of vertebrate genomes. 18566769 - Modeling sequence evolution. 15119449 - Using comparative genomic data to test for fast-x evolution. 12188049 - Expansion of genome coding regions by acquisition of new genes. 19561299 - Programmed loss of millions of base pairs from a vertebrate genome. 17956639 - Analysis of complete mitochondrial genome sequences increases phylogenetic resolution o... 1655739 - Fructose catabolism in xanthomonas campestris pv. campestris. sequence of the pts opero... 9358059 - Identification of adjacent genes encoding the major catalase and a bacterioferritin fro... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 97 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2000 Apr |
Date Detail:
|
Created Date: 2000-05-17 Completed Date: 2000-05-17 Revised Date: 2010-09-13 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 3878-83 Citation Subset: IM; S |
Affiliation:
|
The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
GENBANK/AF242212; AF242213; AF242214; AF242215; AF242216; AF242217; AF242218; AF242219 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Antibodies, Catalytic / administration & dosage, genetics, metabolism* Binding Sites Cell Line Cloning, Molecular Evolution, Molecular* Fructose-Bisphosphate Aldolase / immunology Mice Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Conformation Sequence Homology, Amino Acid |
| Grant Support | |
ID/Acronym/Agency:
|
CA27489/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Catalytic; EC 4.1.2.13/Fructose-Bisphosphate Aldolase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peptide nucleic acids rather than RNA may have been the first genetic molecule.
Next Document: Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model.