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

Kai Gao; Sergey Lunev; Mariska P. M. van den Berg; Zayana M. Al-Dahmani; Stephen Evans; Dyon A. L. J. Mertens; Herman Meurs; Reinoud Gosens; Matthew R. Groves

doi:10.1007/s11033-021-06176-5

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

Kai Gao, Sergey Lunev, Mariska P. M. van den Berg, Zayana M. Al-Dahmani, Stephen Evans, Dyon A. L. J. Mertens, Herman Meurs, Reinoud Gosens, Matthew R. Groves^*

^*Bijbehorende auteur voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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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 IC50 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.

Originele taal-2	English
Pagina's (van-tot)	1959–1966
Aantal pagina's	8
Tijdschrift	Molecular Biology Reports
Volume	48
Nummer van het tijdschrift	2
DOI's	https://doi.org/10.1007/s11033-021-06176-5
Status	Published - 15-feb.-2021

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10.1007/s11033-021-06176-5Licentie: CC BY

A synthetic peptide as an allosteric inhibitor of human arginase I and IIFinal publisher's version, 1,06 MBLicentie: CC BY

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title = "A synthetic peptide as an allosteric inhibitor of human arginase I and II",

abstract = "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 IC50 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.",

keywords = "Arginases, Urea cycle, Peptide analogue, Inhibitor, Microscale Thermophoresis, Colorimetric measurement",

author = "Kai Gao and Sergey Lunev and {van den Berg}, {Mariska P. M.} and Al-Dahmani, {Zayana M.} and Stephen Evans and Mertens, {Dyon A. L. J.} and Herman Meurs and Reinoud Gosens and Groves, {Matthew R.}",

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T1 - A synthetic peptide as an allosteric inhibitor of human arginase I and II

AU - Gao, Kai

AU - Lunev, Sergey

AU - van den Berg, Mariska P. M.

AU - Al-Dahmani, Zayana M.

AU - Evans, Stephen

AU - Mertens, Dyon A. L. J.

AU - Meurs, Herman

AU - Gosens, Reinoud

AU - Groves, Matthew R.

PY - 2021/2/15

Y1 - 2021/2/15

N2 - 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 IC50 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.

AB - 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 IC50 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.

KW - Arginases

KW - Urea cycle

KW - Peptide analogue

KW - Inhibitor

KW - Microscale Thermophoresis

KW - Colorimetric measurement

U2 - 10.1007/s11033-021-06176-5

DO - 10.1007/s11033-021-06176-5

M3 - Article

C2 - 33590412

SN - 0301-4851

VL - 48

SP - 1959

EP - 1966

JO - Molecular Biology Reports

JF - Molecular Biology Reports

IS - 2

ER -