Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme.
Int J Mol Sci
; 23(1)2021 Dec 31.
Article
en En
| MEDLINE
| ID: mdl-35008880
ABSTRACT
APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48-64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptido Hidrolasas
/
Péptidos
Límite:
Humans
Idioma:
En
Año:
2021
Tipo del documento:
Article