STRUCTURAL AND KINETIC EVIDENCE FOR STRAIN IN BIOLOGICAL CATALYSIS

A classic hypothesis for enzyme catalysis is the induction of strain i n the substrate. This notion was first expressed by Haldane with the l ock and key analogy-''the key does not fit the lock perfectly but exer cises a certain strain on it'' (1). This mechanism has often been invo ked to explain the catalytic efficiency of enzymes but has been diffic ult to establish conclusively (2-7). Here we describe X-ray crystallog raphic and mutational studies of an antibody metal chelatase which str ongly support the notion that this antibody catalyzes metal ion insert ion into the porphyrin ring by inducing strain. Analysis of the germli ne precursor suggests that this strain mechanism arose during the proc ess of affinity maturation in response to a conformationally distorted N-alkylmesoporphyrin.