A New Catalytic Site Functioning in Antigen Cleavage by H34 Catalytic Antibody Light Chain

Overview

Journal Sci Rep

Specialty Science

Date 2022 Nov 10

PMID 36357546

Authors

Emi Hifumi

Tamami Nonaka

Hiroaki Taguchi

Taizo Uda

Affiliations

Soon will be listed here.

Abstract

The cleavage reactions of catalytic antibodies are mediated by a serine protease mechanism involving a catalytic triad composed of His, Ser, and Asp residues, which reside in the variable region. Recently, we discovered a catalytic antibody, H34 wild type (H34wt), that is capable of enzymatically cleaving an immune-check point PD-1 peptide and recombinant PD-1; however, H34wt does not contain His residues in the variable region. To clarify the reason behind the catalytic features of H34wt and the amino acid residues involved in the catalytic reaction, we performed site-directed mutagenesis focusing on the amino acid residues involved in the cleavage reaction, followed by catalytic activity tests, immunological reactivity evaluation, and molecular modeling. The results revealed that the cleavage reaction by H34wt proceeds through the action of a new catalytic site composed of Arg, Thr, and Gln. This new scheme differs from that of the serine protease mechanism of catalytic antibodies.

Citing Articles

Enzymatization of mouse monoclonal antibodies to the corresponding catalytic antibodies.

Hifumi E, Ito Y, Tsujita M, Taguchi H, Uda T Sci Rep. 2024; 14(1):12184.

PMID: 38806597 PMC: 11133420. DOI: 10.1038/s41598-024-63116-6.

Direct conversion of a general antibody to its catalytic antibody and corresponding applications -Importance and role of Pro95 in CDR-3.

Hifumi E, Taguchi H, Nonaka T, Uda T Proc Jpn Acad Ser B Phys Biol Sci. 2023; 99(6):155-172.

PMID: 37331814 PMC: 10319470. DOI: 10.2183/pjab.99.010.

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