Benjamin Spiller
Last active: 2/25/2021

Structural and kinetic evidence for strain in biological catalysis.

Romesberg FE, Santarsiero BD, Spiller B, Yin J, Barnes D, Schultz PG, Stevens RC
Biochemistry. 1998 37 (41): 14404-9

PMID: 9772166 · DOI:10.1021/bi981578c

A classic hypothesis for enzyme catalysis is the induction of strain in the substrate. This notion was first expressed by Haldane with the lock and key analogy-"the key does not fit the lock perfectly but exercises a certain strain on it" (1). This mechanism has often been invoked to explain the catalytic efficiency of enzymes but has been difficult to establish conclusively (2-7). Here we describe X-ray crystallographic and mutational studies of an antibody metal chelatase which strongly support the notion that this antibody catalyzes metal ion insertion into the porphyrin ring by inducing strain. Analysis of the germline precursor suggests that this strain mechanism arose during the process of affinity maturation in response to a conformationally distorted N-alkylmesoporphyrin.

MeSH Terms (18)

Amino Acid Sequence Animals Antibodies, Monoclonal Antibody Affinity Catalysis Crystallography, X-Ray Ferrochelatase Haptens Humans Immunoglobulin Fab Fragments Kinetics Mesoporphyrins Mice Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Conformation Recombinant Fusion Proteins

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