Cleavage of Pro-X and Glu-X bonds catalyzed by the branched chain amino acid preferring activity of the bovine pituitary multicatalytic proteinase complex (20S proteasome).
Cleavage of Pro-X and Glu-X bonds catalyzed by the branched chain amino acid preferring activity of the bovine pituitary multicatalytic proteinase complex (20S proteasome).
复制标题
牛垂体多催化蛋白酶复合物（20S 蛋白酶体）的支链氨基酸偏好活性催化 Pro-X 和 Glu-X 键的断裂。
DOI：
10.1006/abbi.1996.0436
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Wilk,S
中科院分区：
文献类型：
--
作者：
Cardozo,C;Chen,WE;Wilk,S
The multicatalytic proteinase complex or 20S proteasome is involved in the extralysosomal degradation of both long- and short-lived proteins. The eukaryotic enzyme is composed of 14 nonidentical subunits arranged as a complex dimer of the composition (α7β7)2. Recent studies identify N-terminal threonines present on some β-subunits as the active-site residues. It has been proposed that the molecule contains three or four proteolytically active subunits [Seemulleret al., Science268, 579–582 (1995)]. Studies with synthetic substrates, activators, and inhibitors, however, have identified at least five distinct catalytic activities. To further characterize the specificity of the previously defined “peptidyl glutamyl peptide bond hydrolyzing activity,”N-benzyloxycarbonyl-Leucyl-Leucyl-Glutamal was synthesized as a potential inhibitor. Surprisingly, this aldehyde most potently inhibited the “branched chain amino acid preferring activity” (BrAAP). To further explore BrAAP specificity, novel substrates containing internal prolyl and glutamyl residues were synthesized. Their use established that the BrAAP activity catalyzed both a postproline and a postglutamate cleavage and therefore has a broader specificity than previously recognized. These results help explain earlier observations on treatment of the multicatalytic proteinase complex with 3,4-dichloroisocoumarin. This reagent activates both the BrAAP activity and the degradation of β-casein and inhibits the other catalytic activities.
