Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1

Zhong Yin Zhang, Ilene M. Reardon, John O. Hui, Kathy L. O’Connell, Roger A. Poorman, Alfredo G. Tomasselli, Robert L. Heinrikson

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 μM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy.

Original languageEnglish (US)
Pages (from-to)8717-8721
Number of pages5
JournalBiochemistry
Volume30
Issue number36
DOIs
StatePublished - Sep 1 1991

Fingerprint

Viruses
Renin
Aspartic Acid Proteases
HIV-1
Zinc
Peptide Hydrolases
Enzymes
HIV Protease
Edetic Acid
Dimers
Catalytic Domain
Acquired Immunodeficiency Syndrome
Hand
Substrates
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Zhang, Z. Y., Reardon, I. M., Hui, J. O., O’Connell, K. L., Poorman, R. A., Tomasselli, A. G., & Heinrikson, R. L. (1991). Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1. Biochemistry, 30(36), 8717-8721. https://doi.org/10.1021/bi00100a001

Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1. / Zhang, Zhong Yin; Reardon, Ilene M.; Hui, John O.; O’Connell, Kathy L.; Poorman, Roger A.; Tomasselli, Alfredo G.; Heinrikson, Robert L.

In: Biochemistry, Vol. 30, No. 36, 01.09.1991, p. 8717-8721.

Research output: Contribution to journalArticle

Zhang, ZY, Reardon, IM, Hui, JO, O’Connell, KL, Poorman, RA, Tomasselli, AG & Heinrikson, RL 1991, 'Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1', Biochemistry, vol. 30, no. 36, pp. 8717-8721. https://doi.org/10.1021/bi00100a001
Zhang ZY, Reardon IM, Hui JO, O’Connell KL, Poorman RA, Tomasselli AG et al. Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1. Biochemistry. 1991 Sep 1;30(36):8717-8721. https://doi.org/10.1021/bi00100a001
Zhang, Zhong Yin ; Reardon, Ilene M. ; Hui, John O. ; O’Connell, Kathy L. ; Poorman, Roger A. ; Tomasselli, Alfredo G. ; Heinrikson, Robert L. / Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1. In: Biochemistry. 1991 ; Vol. 30, No. 36. pp. 8717-8721.
@article{49afcdb090a6472e9a92fe10a9ab4b9d,
title = "Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1",
abstract = "We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 μM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy.",
author = "Zhang, {Zhong Yin} and Reardon, {Ilene M.} and Hui, {John O.} and O’Connell, {Kathy L.} and Poorman, {Roger A.} and Tomasselli, {Alfredo G.} and Heinrikson, {Robert L.}",
year = "1991",
month = "9",
day = "1",
doi = "10.1021/bi00100a001",
language = "English (US)",
volume = "30",
pages = "8717--8721",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "36",

}

TY - JOUR

T1 - Zinc Inhibition of Renin and the Protease from Human Immunodeficiency Virus Type 1

AU - Zhang, Zhong Yin

AU - Reardon, Ilene M.

AU - Hui, John O.

AU - O’Connell, Kathy L.

AU - Poorman, Roger A.

AU - Tomasselli, Alfredo G.

AU - Heinrikson, Robert L.

PY - 1991/9/1

Y1 - 1991/9/1

N2 - We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 μM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy.

AB - We report here for the first time that Zn2+ is an effective inhibitor of renin and the protease from HIV-1, two aspartyl proteinases of considerable physiological importance. Inhibition of renin is noncompetitive and is accompanied by binding of 1 mol of Zn2+/mol of enzyme. Depending on the substrate, inhibition of the HIV protease by Zn2+ can be either competitive or noncompetitive, but in neither case is loss of activity due to disruption of the protease dimer. Inhibition of both enzymes is first order with respect to Zn2+ and is rapidly reversed by addition of EDTA. Ki values are strongly pH dependent and optimal in the range of 20 μM at or above pH 7. All of the data in hand suggest that the inhibitory effect of Zn2+ is a consequence of its binding at, or near, the active-site carboxyl groups of these aspartyl proteinases. This inhibition of the viral enzyme may help to explain some of the beneficial effects seen in AIDS patients who have received Zn2+ therapy.

UR - http://www.scopus.com/inward/record.url?scp=0025787584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025787584&partnerID=8YFLogxK

U2 - 10.1021/bi00100a001

DO - 10.1021/bi00100a001

M3 - Article

C2 - 1888732

AN - SCOPUS:0025787584

VL - 30

SP - 8717

EP - 8721

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 36

ER -