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DC Field | Value | Language |
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dc.contributor.author | Knouch, Nabil | - |
dc.date.accessioned | 2019-11-10T10:57:49Z | - |
dc.date.available | 2019-11-10T10:57:49Z | - |
dc.date.issued | 2006-08-18 | - |
dc.identifier.citation | American Society for Biochemistry and Molecular Biology | en_US |
dc.identifier.uri | http://dspace.univ-bouira.dz:8080/jspui/handle/123456789/6162 | - |
dc.description.abstract | Herein we designed, synthesized, tested, and validated fluorogenic methylcoumarinamide (MCA) and chloromethylketonepeptides spanning the Lassa virus GPC cleavage site as substrates and inhibitors for the proprotein convertase SKI-1/S1P. The 7-mer MCA (YISRRLL-MCA) and 8-mer MCA (IYISRRLLMCA) are very efficiently cleaved with respect to both the 6-mer MCA (ISRRLL-MCA) and point mutated fluorogenic analogues, except for the 7-mer mutant Y253F. The importance of the P7 phenylic residue was confirmed by digestions of two 16-mer non-fluorogenic peptidyl substrates that differ by a single point mutation (Y253A). Because NMR analysis of these 16-mer peptides did not reveal significant structural differences at recognition motif RRLL, the P7 Tyr residue is likely important in establishing key interactions within the catalytic pocket of SKI-1. Based on these data, we established through analysis of proATF6 and pro-SREBP-2 cellular processing that decanoylated chloromethylketone 7-mer, 6-mer, and 4-mer peptides containing the core RRLL sequence are irreversible and potent ex vivo SKI-1 inhibitors. Although caution must be exercised in using these inhibitors in in vitro reactions, as they can also inhibit the basic amino acid-specific convertase furin, within cells and when used at concentrations <100 M these inhibitors are relatively specific for inhibition of SKI-1 processing events, as opposed to those performed by furin-like convertases | en_US |
dc.language.iso | en | en_US |
dc.publisher | university bouira | en_US |
dc.title | The proprotein convertase ski-1/s1p in vitro analysis of lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitors | en_US |
dc.type | Article | en_US |
Appears in Collections: | Articles |
Files in This Item:
File | Description | Size | Format | |
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J. Biol. Chem.-2006-Pasquato-23471-81.pdf | 589,75 kB | Adobe PDF | View/Open |
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