A synthetic peptide as an allosteric inhibitor of human arginase I and II.

Autor: Gao K; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands., Lunev S; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands.; EV Biotech, Groningen, The Netherlands., van den Berg MPM; Immunopharmacology, Department Molecular Pharmacology, University of Groningen, Groningen, The Netherlands., Al-Dahmani ZM; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands.; Immunopharmacology, Department Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.; Molecular Pharmacology, Department of Pharmacy, University of Groningen, Groningen, The Netherlands., Evans S; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands., Mertens DALJ; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands., Meurs H; Molecular Pharmacology, Department of Pharmacy, University of Groningen, Groningen, The Netherlands., Gosens R; Immunopharmacology, Department Molecular Pharmacology, University of Groningen, Groningen, The Netherlands., Groves MR; Structure Biology, Drug Design Group Departments of Pharmacy, University of Groningen, Groningen, The Netherlands. m.r.groves@rug.nl.
Jazyk: angličtina
Zdroj: Molecular biology reports [Mol Biol Rep] 2021 Feb; Vol. 48 (2), pp. 1959-1966. Date of Electronic Publication: 2021 Feb 15.
DOI: 10.1007/s11033-021-06176-5
Abstrakt: Arginine metabolism mediated by arginases plays a critical role in cell and tissue function. The arginine hydrolysis is deeply involved in the urea cycle, which helps the kidney excrete ammonia from blood. Upregulation of arginases affects microenvironment stability due to the presence of excess urea in blood. To regulate the arginase activities properly, a synthetic peptide based on the structure of human arginase I was designed and assessed. Preliminary data shows it inhibits human arginase I and II with an IC 50 of 2.4 ± 0.3 and 1.8 ± 0.1 mmol, respectively. Our kinetic analysis indicates the inhibition is not competitive with substrate - suggesting an allosteric mechanism. This result provides a step towards specific inhibitors design.
Databáze: MEDLINE
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