Interaction between human alpha2-macroglobulin and duodenase, a serine proteinase with dual specificity.
Interaction between a serine proteinase from bovine duodenum and human serum alpha(2)-macroglobulin (alpha(2)-MG) was studied. alpha(2)-MG is established to be one of the most effective duodenase inhibitors. The enzyme is completely inhibited in less than 30 sec at equimolar ratio of the inhibitor and enzyme (concentration 2 x 10(-8) M). Under identical conditions, the rate of duodenase association with alpha(2)-MG is at least 2.5-fold higher than the rate of chymotrypsin association with this inhibitor. The interaction with duodenase results in proteolysis of the inhibitor subunit in the "bait region". Similarly to other proteases, duodenase in the complex with alpha(2)-MG retains the intact catalytic apparatus and ability to hydrolyze some small substrates. But the duodenase-inhibitor complex is fully inactive to proteins (bovine serum albumin). The stoichiometry of the enzyme interaction with the inhibitor is 2 : 1 (mol/mol). Based on the association rate constant and the termination time of the duodenase and alpha(2)-MG in vivo association, alpha(2)-MG is suggested to be a physiological regulator of the enzyme.
Denisenko
O O
OO
Department of Chemical Enzymology, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119992, Russia. nilar@enzyme.chem.msu.ru.
Zamolodchikova
T S
TS
Popykina
N A
NA
Larionova
N I
NI
D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D013379:Substrate Specificity; D000511:alpha-Macroglobulins / Q000378:metabolism*
D046912:Multiprotein Complexes; D015842:Serine Proteinase Inhibitors; D000511:alpha-Macroglobulins; D012697:Serine Endopeptidases; C078261:duodenase