title: Interaction of subtilisins with serpins.
abstract: Serpins are well-characterized inhibitors of the chymotrypsin family serine proteinases. We have investigated the interaction of two serpins with members of the subtilisin family, proteinases that possess a similar catalytic mechanism to the chymotrypsins, but a totally different scaffold. We demonstrate that alpha 1 proteinase inhibitor inhibits subtilisin Carlsberg and proteinase K, and alpha 1 antichymotrypsin inhibits proteinase K, but not subtilisin Carlsberg. When inhibition occurs, the rate of formation and stability of the complexes are similar to those formed between serpins and chymotrypsin family members. However, inhibition of subtilisins is characterized by large partition ratios where more than four molecules of each serpin are required to inhibit one subtilisin molecule. The partition ratio is caused by the serpins acting as substrates or inhibitors. The ratio decreases as temperature is elevated in the range 0-45 degrees C, indicating that the serpins are more efficient inhibitors at high temperature. These aspects of the subtilisin interaction are all observed during inhibition of chymotrypsin family members by serpins, indicating that serpins accomplish inhibition of these two distinct proteinase families by the same mechanism.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: T
authors.initials: T
authors.lastname: Komiyama
authors.forename: H
authors.initials: H
authors.lastname: Grøn
authors.forename: P A
authors.initials: PA
authors.lastname: Pemberton
authors.forename: G S
authors.initials: GS
authors.lastname: Salvesen
mesh_terms: D000595:Amino Acid Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D019286:Endopeptidase K / Q000737:chemistry / Q000494:pharmacology*; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D013381:Subtilisins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013696:Temperature; D000514:alpha 1-Antichymotrypsin / Q000737:chemistry / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000514:alpha 1-Antichymotrypsin; D000515:alpha 1-Antitrypsin; D013381:Subtilisins; D019286:Endopeptidase K