Biochemistry (Moscow)

, Volume 74, Issue 12, pp 1382–1387 | Cite as

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

  • S. S. Sen
  • N. R. Bhuyan
  • K. Lakshman
  • A. K. Roy
  • B. Chakraborty
  • T. BeraEmail author


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.

Key words

Leishmania donovani promastigote and amastigote pyrophosphatase ATPase plasma membrane imidodiphosphate verapamil 



adenosine triphosphatase








phenylarsine oxide








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Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • S. S. Sen
    • 1
  • N. R. Bhuyan
    • 2
  • K. Lakshman
    • 3
  • A. K. Roy
    • 1
  • B. Chakraborty
    • 1
  • T. Bera
    • 1
    Email author
  1. 1.Division of Medicinal Biochemistry, Department of Pharmaceutical TechnologyJadavpur UniversityKolkataIndia
  2. 2.Department of Pharmaceutical ChemistryHimalayan Pharmacy InstituteMajhitar, Rangpo, SikkimIndia
  3. 3.Department of PharmacognosyP. E. S. College of PharmacyHanumanthnagar BangaloreIndia

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