Adenanthin targets proteins involved in the regulation of disulphide bonds
PBN-AR
Instytucja
Instytut Chemii Organicznej Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
BIOCHEMICAL PHARMACOLOGY
ISSN
0006-2952
EISSN
1873-2968
Wydawca
PERGAMON-ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2014
Numer zeszytu
2
Strony od-do
210-216
Numer tomu
89
Identyfikator DOI
Liczba arkuszy
7.00
Słowa kluczowe
en
Adenanthin; Cancer; Peroxiredoxin; Protein disulphide isomerase; Thioredoxin
Streszczenia
Język
en
Treść
Adenanthin has been recently shown to inhibit the enzymatic activities of peroxiredoxins (Prdx) I and II through its functional a,b-unsaturated ketone group serving as a Michael acceptor. A similar group is found in SK053, a compound recently developed by our group to target the thioredoxin–thioredoxin reductase (Trx–TrxR) system. This work provides evidence that next to Prdx I and II adenanthin targets additional proteins including thioredoxin–thioredoxin reductase system as well as protein disulfide isomerase (PDI) that contain a characteristic structural motif, referred to as a thioredoxin fold. Adenanthin inhibits the activity of Trx-TR system and PDI in vitro in the insulin reduction assay and decreases the activity of Trx in cultured cells. Moreover, we identified Trx-1 as an adenanthin binding protein in cells incubated with biotinylated adenanthin as an affinity probe. The results of our studies indicate that adenanthin is a mechanism-selective, rather than an enzyme-specific inhibitor of enzymes containing readily accessible, nucleophilic cysteines. This observation might be of importance in considering potential therapeutic applications of adenanthin to include a range of diseases, where aberrant activity of Prdx, Trx–TrxR and PDI is involved in their pathogenesis.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
656678
CrossrefMetadata from Crossref logo
Cytowania
Liczba prac cytujących tę pracę
Brak danych
Referencje
Liczba prac cytowanych przez tę pracę
Brak danych