ArticleProceedings of the National Academy of Sciences of the United States of America1990
Antibody remodeling: a general solution to the design of a metal-coordination site in an antibody binding pocket.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1990. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 114 citations in OpenAlex.
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Robust Production, Crystallization, Structure Determination, and Analysis of [Fe-S] Proteins: Uncovering Control of Electron Shuttling and Gating in the Respiratory Metabolism of Molybdopterin Guanine Dinucleotide Enzymes.Methods in enzymology · 2018Article
- Emerging critical roles of Fe-S clusters in DNA replication and repair.Biochimica et biophysica acta · 2015Review
- 2D IR spectroscopy of histidine: probing side-chain structure and dynamics via backbone amide vibrations.The journal of physical chemistry. B · 2014Article
- OptGraft: A computational procedure for transferring a binding site onto an existing protein scaffold.Protein science : a publication of the Protein Society · 2009Article
- Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.Chemical reviews · 2008Review
- Interfacial metal and antibody recognition.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- A cofactor approach to copper-dependent catalytic antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- On the failure of de novo-designed peptides as biocatalysts.Proceedings of the National Academy of Sciences of the United States of America · 1996Review
- Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II.The Journal of experimental medicine · 1995Article
- Scorpion toxins as natural scaffolds for protein engineering.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations.The EMBO journal · 1995Article
- Structure-assisted redesign of a protein-zinc-binding site with femtomolar affinity.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- The biotechnology and applications of antibody engineering.Molecular biotechnology · 1995Review
- Dissection of an antibody-catalyzed reaction.Proceedings of the National Academy of Sciences of the United States of America · 1994Review
- Direct selection of antibodies that coordinate metals from semisynthetic combinatorial libraries.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
- A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
- Nucleotide sequence analysis of CDR3 elements of a panel of anti-peptide monoclonal antibodies recognizing parathyroid hormone-related protein.Immunology · 1993Article
- Structural biology and diabetes mellitus: molecular pathogenesis and rational drug design.Diabetologia · 1992Review
- Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen.The Journal of experimental medicine · 1992Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
To develop a general approach to designing cofactor-binding sites for catalytic antibodies, we characterized structural patterns in the binding sites of antibodies and zinc enzymes. Superposition of eight sets of antibody light- and heavy-chain variable domains identified structurally conserved sites within the sequence-variable complementarity determining regions. The pattern for catalytic zinc sites included two ligands close in sequence, a sequence-distant ligand, and a main-chain hydrogen bond joining two ligands. In both the light- and heavy-chain variable domains, the stereochemistry of five structurally conserved sites general to all known antibody structures matched that of the zinc ligands of carbonic anhydrase: three residues on two hydrogen-bonded antiparallel beta-strands. For one such general site, an antibody model replacing residue 34 on the first complementarity determining region of the light chain (L1) and residues 89 and 91 on the third complementarity determining region of the light chain (L3) with histidine ligands formed a zinc-binding site with an open coordination position at the bottom of the antibody binding pocket. For the anti-fluorescein antibody 4-4-20, this L1-L3 site placed the zinc ion about 4 A from the bound fluorescein, an indicator for metal binding. This predicted zinc-binding mutant was created in the single-chain variable domain construct, expressed, and found by fluorescence quenching to bind metal ion with an affinity constant of 10(6) M-1. Thus, our template-based multisite design proved successful for remodeling an antibody to contain a cofactor-binding site, without requiring further mutagenesis and screening. Combination of a specific light or heavy chain containing a catalytic metal site with a library of complementary chains raised to potential substrates or transition state analogs should greatly improve the production of catalytic antibodies with desired activities and specificities.
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