A monoclonal antibody that triggers deacylation of an intermediate thrombin-antithrombin III complex.
Upon incubation of antithrombin III with thrombin in the presence of a monoclonal antibody recognizing an epitope exposed on the heavy chain part of thrombin-cleaved two-chain antithrombin III, antithrombin III was preferentially cleaved by the enzyme as a substrate, rather than covalently complexed with the enzyme to form an equimolar, stable acyl complex. Once the stable acyl complex was formed between the enzyme and antithrombin III, however, no further liberation of two-chain antithrombin III was observed. Kinetic studies showed that heparin does not affect this reaction, although generation of thrombin-cleaved two-chain antithrombin III is apparently accelerated in accordance with the rate constant for heparin-enhanced thrombin-antithrombin III complex formation. Here we propose the term "switching antibody" for an antibody that triggers deacylation of an intermediate enzyme-inhibitor complex by switching the enzyme-inhibitor reaction from the major pathway of stable acyl complex formation to an alternative pathway of cleavage of the inhibitor as a substrate.
Asakura
S
S
Division of Hemostasis and Thrombosis Research, Institute of Hematology, Jichi Medical School, Tochigi-Ken, Japan.
Matsuda
M
M
Yoshida
N
N
Terukina
S
S
Kihara
H
H
D000911:Antibodies, Monoclonal; D000990:Antithrombin III / Q000276:immunology / Q000378:metabolism*; D002850:Chromatography, Gel; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007074:Immunoglobulin G; D007700:Kinetics; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases