title: Structural evidence for substrate strain in antibody catalysis.
abstract: The crystal structure of the Michaelis complex between the Fab fragment of ferrochelatase antibody 7G12 and its substrate mesoporphyrin has been solved to 2.6-A resolution. The antibody-bound mesoporphyrin clearly adopts a nonplanar conformation and reveals that the antibody catalyzes the porphyrin metallation reaction by straining/distorting the bound substrate toward the transition-state configuration. The crystal structures of the Fab fragment of the germ-line precursor antibody to 7G12 and its complex with the hapten N-methylmesoporphyrin have also been solved. A comparison of these structures with the corresponding structures of the affinity-matured antibody 7G12 reveals the molecular mechanism by which the immune system evolves binding energy to catalyze this reaction.
authors.affiliation: Department of Chemistry, University of California, Berkeley, CA 94720, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Scott E
authors.initials: SE
authors.lastname: Andryski
authors.forename: Albert E
authors.initials: AE
authors.lastname: Beuscher
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Stevens
authors.forename: Peter G
authors.initials: PG
authors.lastname: Schultz
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006241:Haptens / Q000737:chemistry; D007700:Kinetics; D008652:Mesoporphyrins / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D055672:Static Electricity; D013379:Substrate Specificity
chemical_list: D000906:Antibodies; D006241:Haptens; D008652:Mesoporphyrins; C031468:mesoporphyrin IX