A new catalytic site functioning in antigen cleavage by H34 catalytic antibody light chain.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 11 2022
10 11 2022
Historique:
received:
09
06
2022
accepted:
03
11
2022
entrez:
10
11
2022
pubmed:
11
11
2022
medline:
15
11
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36357546
doi: 10.1038/s41598-022-23689-6
pii: 10.1038/s41598-022-23689-6
pmc: PMC9649737
doi:
Substances chimiques
Antibodies, Catalytic
0
Programmed Cell Death 1 Receptor
0
Immunoglobulin Light Chains
0
Serine Endopeptidases
EC 3.4.21.-
Amino Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19185Informations de copyright
© 2022. The Author(s).
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