Inhibition-mediated changes in prolyl oligopeptidase dynamics possibly related to α-synuclein aggregation

Abstract

The formation of protein aggregates is one of the leading causes of neuronal malfunction and subsequent brain damage in many neurodegenerative diseases. In Parkinson's disease, α-synucleins are involved in the...

VHL-Modified PROteolysis TArgeting Chimeras (PROTACs) as a Strategy to Evade Metabolic Degradation in In Vitro Applications

“…39 PEP is a dimer catabolizing proline-containing polypeptides with a maximum length of 30 amino acids. 37,42 include oxytocin, angiotensin II, 46 bradykinin, 37 and also neuropeptides. 39,47 The catalytic triad (Ser554, His680, and Asp641) is located in the α/β hydrolase domain at the interface with the β-propeller domain.…”

“…PEPs have both enzymatic and nonenzymatic functions . The latter have been deeply studied in the brain as their alteration has been linked to the onset of neurodegenerative diseases. − Increased mRNA transcripts of PEP have also been detected in certain cancerous tissues …”

“…PEP is a dimer catabolizing proline-containing polypeptides with a maximum length of 30 amino acids. , Substrates of PEP include oxytocin, angiotensin II, bradykinin, and also neuropeptides. , …”

“…The catalytic triad (Ser554, His680, and Asp641) is located in the α/β hydrolase domain at the interface with the β-propeller domain. The latter is formed by seven blades creating a central tunnel oriented toward the catalytic triad. ,,− A thiol group in the active site is noteworthy, and its presence is crucial for enzyme activity …”

“…Known since 1983, , PEPs are serine proteases diversely expressed in many human tissues; they are mainly cytosolic, but activity has also been found in the cell membranes . PEPs have both enzymatic and nonenzymatic functions . The latter have been deeply studied in the brain as their alteration has been linked to the onset of neurodegenerative diseases. − Increased mRNA transcripts of PEP have also been detected in certain cancerous tissues …”