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Membrane bound pyrophosphatase and P-Type adenosine triphosphatase of Leishmania donovani as possible chemotherapeutic targets: Similarities and differences in inhibitor sensitivities

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Abstract

The activities of inorganic pyrophosphatase (PPase) and adenosine triphosphatase (ATPase) were studied in the plasma membrane of Leishmania donovani promastigotes and amastigotes. It was shown that the specific activity of PPase was greater than that of ATPase in the promastigote plasma membrane. We characterized H+-PPase present in the plasma membrane of L. donovani and investigated its possible role in the survival of promastigote and amastigote. PPase activity was stimulated by K+ and sodium orthovanadate and inhibited by pyrophosphate analogs (imidodiphosphate and alendronate), KF, N,N′-dicyclohexylcarbodiimide (DCCD), thiol reagents (p-chloromercuribenzenesulfonate (PCMBS), N-ethylmaleimide (NEM), and phenylarsine oxide (PAO)), the ABC superfamily transport modulator verapamil, and also by the F1Fo-ATPase inhibitor quercetin. ATPase activity was stimulated by K+ and verapamil, inhibited by DCCD, PCMBS, NEM, sodium azide, sodium orthovanadate, and quercetin, and was unaffected by PAO. We conclude that there are significant differences within promastigote, amastigote, and mammalian host in cytosolic pH homeostasis to merit the inclusion of PPase transporter as a putative target for rational drug design.

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Abbreviations

ATPase:

adenosine triphosphatase

DCCD:

N,N′-dicyclohexylcarbodiimide

IDP:

imidodiphosphate

NEM:

N-ethylmaleimide

PAO:

phenylarsine oxide

PCMBS:

p-chloromercuribenzenesulfonate

PPase:

pyrophosphatase

PPi :

pyrophosphate

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Authors and Affiliations

  1. Division of Medicinal Biochemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 7000032, India

    S. S. Sen, A. K. Roy, B. Chakraborty & T. Bera

  2. Department of Pharmaceutical Chemistry, Himalayan Pharmacy Institute, Majhitar, Rangpo, Sikkim, 737136, India

    N. R. Bhuyan

  3. Department of Pharmacognosy, P. E. S. College of Pharmacy, Hanumanthnagar Bangalore, 560050, India

    K. Lakshman

Authors
  1. S. S. Sen
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  2. N. R. Bhuyan
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  3. K. Lakshman
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  4. A. K. Roy
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  5. B. Chakraborty
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  6. T. Bera
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Correspondence to T. Bera.

Additional information

Published in Russian in Biokhimiya, 2009, Vol. 74, No. 12, pp. 1695–1702.

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Sen, S.S., Bhuyan, N.R., Lakshman, K. et al. Membrane bound pyrophosphatase and P-Type adenosine triphosphatase of Leishmania donovani as possible chemotherapeutic targets: Similarities and differences in inhibitor sensitivities. Biochemistry Moscow 74, 1382–1387 (2009). https://doi.org/10.1134/S000629790912013X

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  • DOI: https://doi.org/10.1134/S000629790912013X

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