Studies of Inhibitory Mechanisms of Propeptide-Like Cysteine Protease Inhibitors
Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75)...
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| Veröffentlicht in: | Enzyme Research 2014, Vol.2014 (2014), p.250-259 |
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| creator | Nga, Bui T. T. Takeshita, Yuki Yamamoto, Misa Yamamoto, Yoshimi |
| description | Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75), which is essential for its inhibitory potency. The CTLA-2α monomer was converted to a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. The different inhibition mechanisms and functional considerations of these inhibitors are discussed. |
| doi_str_mv | 10.1155/2014/848937 |
| format | Article |
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T. ; Takeshita, Yuki ; Yamamoto, Misa ; Yamamoto, Yoshimi</creator><contributor>Ohshima, Toshihisa</contributor><creatorcontrib>Nga, Bui T. T. ; Takeshita, Yuki ; Yamamoto, Misa ; Yamamoto, Yoshimi ; Ohshima, Toshihisa</creatorcontrib><description>Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75), which is essential for its inhibitory potency. The CTLA-2α monomer was converted to a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. The different inhibition mechanisms and functional considerations of these inhibitors are discussed.</description><identifier>ISSN: 2090-0414</identifier><identifier>ISSN: 2090-0406</identifier><identifier>EISSN: 2090-0414</identifier><identifier>DOI: 10.1155/2014/848937</identifier><identifier>PMID: 25045530</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Limiteds</publisher><subject>Amino acids ; Bacteriology ; Comparative analysis ; Enzymes ; Insects ; Methods ; Mutagenesis ; Protease inhibitors ; Protein research ; Proteins ; Regulation ; Studies</subject><ispartof>Enzyme Research, 2014, Vol.2014 (2014), p.250-259</ispartof><rights>Copyright © 2014 Bui T. T. Nga et al.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 Bui T. T. Nga et al. Bui T. T. Nga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Bui T. T. Nga et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a5177-1f60ee00c5cc806a88c2d8a98b363f218b9ed68d0d77bafe42817ffd4755bdf73</citedby><cites>FETCH-LOGICAL-a5177-1f60ee00c5cc806a88c2d8a98b363f218b9ed68d0d77bafe42817ffd4755bdf73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089206/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089206/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25045530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ohshima, Toshihisa</contributor><creatorcontrib>Nga, Bui T. T.</creatorcontrib><creatorcontrib>Takeshita, Yuki</creatorcontrib><creatorcontrib>Yamamoto, Misa</creatorcontrib><creatorcontrib>Yamamoto, Yoshimi</creatorcontrib><title>Studies of Inhibitory Mechanisms of Propeptide-Like Cysteine Protease Inhibitors</title><title>Enzyme Research</title><addtitle>Enzyme Res</addtitle><description>Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75), which is essential for its inhibitory potency. The CTLA-2α monomer was converted to a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. 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The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. 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| subjects | Amino acids Bacteriology Comparative analysis Enzymes Insects Methods Mutagenesis Protease inhibitors Protein research Proteins Regulation Studies |
| title | Studies of Inhibitory Mechanisms of Propeptide-Like Cysteine Protease Inhibitors |
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