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- Proteolytic Activation Of Recombinant Pro-memapsin 2018
- Proteolytic Activation Of Recombinant Pro-memapsin 2
- Proteolytic Activation Of Recombinant Pro-memapsin 2017
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Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104
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Proteolytic activation of recombinant pro‐memapsin 2 (pro‐beta‐secretase) studied with new fluorogenic substrates. Ermolieff, Ermolieff; Loy, Loy; Koelsch, Koelsch; Tang, Tang. Crystal structure of memapsin 2 (beta‐secretase) in complex with an inhibitor OM00‐3. 2 ABSTRACT The proteolytic activation of pro-MMP-9 by conversion of 92-kDa precursor into 82-kDa active form has been observed in chronic wounds, tumor metastasis and many. Recombinant TIMP-1 could block the activation of pro-MMP-9 by either the intact skin or skin fractions. Thus, these studies suggest a novel regulation for the proteolytic. Lumenal extension of BACE1 interacts with the catalytic domain opposite of the active site. (A) Depiction scheme of BACE1 (B,C), Protein Data Bank code 1FKN; and pepsin (D,E), Protein Data Bank code 1PSO. The catalytic domain of BACE1 is depicted in light blue and a portion of BACE1 lumenal extension visible in the 1FKN ctrystal structure is depicted in green.
Proteolytic Activation Of Recombinant Pro-memapsin 2018
![Activation Activation](/uploads/1/2/6/5/126588840/563040746.jpg)
Abstract
Proteolytic Activation Of Recombinant Pro-memapsin 2
Memapsin 2 (β-secretase), a membrane-anchored aspartic protease, is involved in the cleavage of β-amyloid precursor protein to form β-amyloid peptide. The primary structure of memapsin 2 suggests that it is synthesized in vivo as pro-memapsin 2 and converted to memapsin 2 by an activating protease [Lin et al. (2000) Proc. Natl. Acad. Sci. U.S.A.97, 1456−1460]. To simulate this activation mechanism and to produce stable mature memapsin 2 for kinetic/specificity studies, we have investigated the activation of recombinant pro-memapsin 2 by several proteases with trypsin-like specificity. Clostripain, kallikrein, and trypsin increased the activity of pro-memapsin 2. Clostripain activation was accompanied by the cleavage of the pro region to form mainly two activation products, Leu30p- and Gly45p-memapsin 2. Another activation product, Leu28p-memapsin 2, was also purified. Kinetics of the activated memapsin 2 were compared with pro-memapsin 2 using two new fluorogenic substrates, Arg-Glu(5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid (EDANS))-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys(4-(4-dimethylaminophenylazo)benzoic acid (DABCYL))-Arg and (7-methoxycoumarin-4-yl)acetyl (MCA))-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys(2,4-dinitrophenyl (DNP)). These results establish that the activity of pro-memapsin 2 stems from a part-time and reversible uncovering of its active site by its pro region. Proteolytic removal of part of the pro-peptide at Leu28p or Gly45p, which diminishes the affinity of the shortened pro-peptide to the active site, results in activated memapsin 2. These results also suggest that Glu33p-memapsin 2 observed in the cells expressing this enzyme [Vassar et al. (1999) Science286, 735−741; Yan et al. (1999) Nature402, 533−537] is an active intermediate of in vivo activation, or that the peptide Glu33p−Arg44p may serve a regulatory role.
![Proteolytic Activation Of Recombinant Pro-memapsin 2 Proteolytic Activation Of Recombinant Pro-memapsin 2](/uploads/1/2/6/5/126588840/231794451.jpg)
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