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

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 ure...

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Autores principales: Gao, Kai, Lunev, Sergey, van den Berg, Mariska P. M., Al-Dahmani, Zayana M., Evans, Stephen, Mertens, Dyon A. L. J., Meurs, Herman, Gosens, Reinoud, Groves, Matthew R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2021
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925462/
https://www.ncbi.nlm.nih.gov/pubmed/33590412
http://dx.doi.org/10.1007/s11033-021-06176-5
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author Gao, Kai
Lunev, Sergey
van den Berg, Mariska P. M.
Al-Dahmani, Zayana M.
Evans, Stephen
Mertens, Dyon A. L. J.
Meurs, Herman
Gosens, Reinoud
Groves, Matthew R.
author_facet Gao, Kai
Lunev, Sergey
van den Berg, Mariska P. M.
Al-Dahmani, Zayana M.
Evans, Stephen
Mertens, Dyon A. L. J.
Meurs, Herman
Gosens, Reinoud
Groves, Matthew R.
author_sort Gao, Kai
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11033-021-06176-5.
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spelling pubmed-79254622021-03-19 A synthetic peptide as an allosteric inhibitor of human arginase I and II Gao, Kai Lunev, Sergey van den Berg, Mariska P. M. Al-Dahmani, Zayana M. Evans, Stephen Mertens, Dyon A. L. J. Meurs, Herman Gosens, Reinoud Groves, Matthew R. Mol Biol Rep Short Communication 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11033-021-06176-5. Springer Netherlands 2021-02-15 2021 /pmc/articles/PMC7925462/ /pubmed/33590412 http://dx.doi.org/10.1007/s11033-021-06176-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Short Communication
Gao, Kai
Lunev, Sergey
van den Berg, Mariska P. M.
Al-Dahmani, Zayana M.
Evans, Stephen
Mertens, Dyon A. L. J.
Meurs, Herman
Gosens, Reinoud
Groves, Matthew R.
A synthetic peptide as an allosteric inhibitor of human arginase I and II
title A synthetic peptide as an allosteric inhibitor of human arginase I and II
title_full A synthetic peptide as an allosteric inhibitor of human arginase I and II
title_fullStr A synthetic peptide as an allosteric inhibitor of human arginase I and II
title_full_unstemmed A synthetic peptide as an allosteric inhibitor of human arginase I and II
title_short A synthetic peptide as an allosteric inhibitor of human arginase I and II
title_sort synthetic peptide as an allosteric inhibitor of human arginase i and ii
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925462/
https://www.ncbi.nlm.nih.gov/pubmed/33590412
http://dx.doi.org/10.1007/s11033-021-06176-5
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