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ARS Home » Plains Area » Manhattan, Kansas » Center for Grain and Animal Health Research » Stored Product Insect and Engineering Research » Research » Publications at this Location » Publication #369860

Research Project: Sustainable Management Strategies for Stored-Product Insects

Location: Stored Product Insect and Engineering Research

Title: Human proline specific peptidases: a systemic analysis

item DUNAEVSKY, YAKOV - Moscow State University
item TERESHCHENKOVA, VALERIIA - Moscow State University
item Oppert, Brenda
item BELOZERSKY, MIKHAIL - Moscow State University
item FILIPPOVA, IRINA - Moscow State University
item ELPIDINA, ELENA - Moscow State University

Submitted to: Biochimica et Biophysica Acta
Publication Type: Review Article
Publication Acceptance Date: 5/14/2020
Publication Date: 5/17/2020
Citation: Dunaevsky, Y.E., Tereshchenkova, V.F., Oppert, B.S., Belozersky, M.A., Filippova, I.Y., Elpidina, E.N. 2020. Human proline specific peptidases: a systemic analysis. Biochimica et Biophysica Acta. 1864(9):129636.

Interpretive Summary: Proline-specific peptidases (PSPs) are enzymes that cut peptides when there is a proline amino acid in the chain. There have been many articles describing PSPs in animals, as they have important biological activities. We review the literature that describe PSPs in humans, important because such a comprehensive review has not been written since the sequencing of the human genome. We find that in addition to a typical enzyme activity in which a peptide chain is cut, PSPs also apparently function by binding to other proteins and thus have a regulatory role in some biological activities. This information has particular relevance because PSPs are involved in human disease, and new therapeutics targeting the enzyme in the form of inhibitors or genetic interventions to control the expression of genes encoding PSPs offer new approaches to treating these diseases.

Technical Abstract: Background: Proline-specific peptidases (PSPs) are a unique group of enzymes that specifically cleave bonds formed by a proline residue. The study of PSPs is important due to their role in the maturation and degradation of peptide hormones and neuropeptides. In addition, changes in PSP activity levels can result in pathological conditions, including various types of cancer. Scope of review: PSPs in mammals, including human, were compared and classified according to data on their physicochemical and biochemical features and possible functional roles in vital processes. In addition to catalytic activity in PSPs, we discuss a non-enzymatic function due to binding with specific ligands that may regulate cellular activity. Major conclusions: PSPs apparently have multiple functions. Two functions rely on the catalytic activity of the enzyme: one involved in a regulatory pathway associated with the ability of many PSPs to hydrolyze peptide hormones and neuropeptides, and the other involved in the trophic pathway associated with the proteolysis of total cellular protein or Pro-rich dietary protein in the digestive tract. PSPs are underestimated as a unique component of the normal human peptidase degradome, providing the body with free proline. PSPs also participate in signal transduction without proteolytic activity, providing the majority of PSPs the ability to form protein-protein interactions that trigger or facilitate the performance of certain functions. General significance: A comparative analysis of PSPs can guide research related to developing inhibitors that counteract the abnormalities associated with changes in PSP activity, and identify true natural substrates of PSPs that will be a key step in understanding exact functions and mechanisms of the action of PSPs in biological processes and disease.