Theory of proteolytic antibody occurrence.
Antibodies (Abs) with proteolytic and other catalytic activities have been characterized in the blood and mucosal secretions of humans and experimental animals. The catalytic activity can be traced to nucleophilic sites of innate origin located in Ab germline variable regions. Discoveries of the natural chemical reactivity of Abs were initially met with bewilderment, as the notion had taken hold that catalytic activities can be introduced into Abs by artificial means, but somatically operative selection pressures are designed only to adapt non-covalent Ab binding to antigen ground states. Unsurprisingly, initial efforts to engineer Abs with catalytic activity were oriented towards improving the non-covalent binding at the atoms immediately within the transition state reaction center. Slowly, however, dogmatic approaches to Ab catalysis have given way to the realization that efficient and specific catalytic Abs can be prepared by improving the natural nucleophilic reactivity combined with non-covalent recognition of epitope regions remote from the reaction center. The field remains beset, however, with controversy. This article attempts to provide a rational basis for natural Ab catalysis, in the hope that understanding this phenomenon will stimulate medical and basic science advances in the field.
Paul
Sudhir
S
Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, 77030, USA. Sudhir.Paul@uth.tmc.edu
Nishiyama
Yasuhiro
Y
Planque
Stephanie
S
Taguchi
Hiroaki
H
D000818:Animals; D017151:Antibodies, Catalytic / Q000502:physiology*; D002384:Catalysis; D006801:Humans; D007113:Immunity, Innate; D008962:Models, Theoretical
D017151:Antibodies, Catalytic