Investigation of an antibody-ligase. Evidence for strain-induced catalysis.
Catalytic antibody 16G3, a peptide ligase with extended substrate scope has been characterized mechanistically exploiting a set of systematically designed perspective substrates 6-9, two of which, thioesters 8 and 9 act instead as inhibitors. Taken together the structure/activity relationships suggest a catalytic mechanism dependent on induction of strain, programmed via specific structural deviations between the hapten and the substrates. General mechanistic implications for de novo induced catalysis are presented.
Savinov
Sergey N
SN
Department of Chemistry, University of Pennsylvania, Philadelphia 19104, USA.
Hirschmann
Ralph
R
Benkovic
Stephen J
SJ
Smith
Amos B
AB
D000906:Antibodies / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002384:Catalysis; D007136:Immunoglobulins / Q000737:chemistry; D007700:Kinetics; D008025:Ligases / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D010455:Peptides; D008025:Ligases