Nucleophilic proteolytic antibodies.
Proteolytic antibodies appear to utilize catalytic mechanisms akin to nonantibody serine proteases, assessed from mutagenesis and protease-inhibitor studies. The catalytic efficiency derives substantially from the ability to recognize the ground state with high affinity. Because the proteolytic activity is germline-encoded, catalysts with specificity for virtually any target polypeptide could potentially be developed by applying appropriate immunogens and selection strategies. Analysis of transition-state stabilizing interactions suggests that chemical reactivity of active-site serine residues is an important contributor to catalysis. A prototype antigen analog capable of reacting covalently with nucleophilic serine residues permitted enrichment of the catalysts from a phage-displayed lupus light-chain library. Further mechanistic developments in understanding proteolytic antibodies may lead to the isolation of catalysts suitable for passive immunotherapy of major diseases, and elicitation of catalytic immunity as a component of prophylactic vaccination.
Gololobov
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G
University of Texas Houston Medical School, Department of Pathology and Laboratory Medicine, 77030, USA. Gennady.V.Gololobov@uth.tmc.edu
Tramontano
A
A
Paul
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S
D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000916:Antibody Diversity; D000941:Antigens / Q000737:chemistry; D001665:Binding Sites; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007700:Kinetics; D012694:Serine / Q000737:chemistry; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism; D013816:Thermodynamics
D017151:Antibodies, Catalytic; D000941:Antigens; D012694:Serine; D012697:Serine Endopeptidases