title: Protein disulfide isomerases exploit synergy between catalytic and specific binding domains.
abstract: Protein disulfide isomerases (PDIs) catalyse the formation of native disulfide bonds in protein folding pathways. The key steps involve disulfide formation and isomerization in compact folding intermediates. The high-resolution structures of the a and b domains of PDI are now known, and the overall domain architecture of PDI and its homologues can be inferred. The isolated a and a' domains of PDI are good catalysts of simple thiol-disulfide interchange reactions but require additional domains to be effective as catalysts of the rate-limiting disulfide isomerizations in protein folding pathways. The b' domain of PDI has a specific binding site for peptides and its binding properties differ in specificity between members of the PDI family. A model of PDI function can be deduced in which the domains function synergically: the b' domain binds unstructured regions of polypeptide, while the a and a' domains catalyse the chemical isomerization steps.
authors.affiliation: Department of Biosciences, University of Kent, Canterbury CT2 7NJ, UK. r.b.freedman@ukc.ac.uk
authors.forename: Robert B
authors.initials: RB
authors.lastname: Freedman
authors.forename: Peter
authors.initials: P
authors.lastname: Klappa
authors.forename: Lloyd W
authors.initials: LW
authors.lastname: Ruddock
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology*; D002384:Catalysis; D020134:Catalytic Domain / Q000502:physiology*; D006801:Humans; D010088:Oxidoreductases / Q000502:physiology; D019704:Protein Disulfide-Isomerases / Q000502:physiology*; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000502:physiology; D013879:Thioredoxins / Q000494:pharmacology
chemical_list: D013879:Thioredoxins; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases