Influence of Mutations of Conserved Arginines on Neuropeptide Binding in the DPP III Active Site.

ABSTRACT: Dipeptidyl peptidase III (DPP III), a zinc exopeptidase, is involved in the final steps of intercellular protein degradation and has a marked affinity for opioid peptides such as enkephalins and endomorphins. Recently, we characterized a number of neuropeptides as potential substrates and inhibitors of human DPP III and provided an explanation for their differential behavior. These studies prompted us to investigate the influence of the conserved R399 and R669 on neuropeptides binding to DPP III. Measuring kinetic parameters in inhibitory assays, we found that mutation of R669 to Ala or Met significantly reduced the inhibitory properties of the slow substrates tynorphin and valorphin, whereas the effects on binding of the good substrates Arg₂-2NA and Leu-enkephalin were small. M

SUBMITTER: Tomic A 

PROVIDER: S-EPMC9967118 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature