Two inhibitors of yeast plasma membrane ATPase 1 (ScPma1p): toward the development of novel antifungal therapies

Sabine Ottilie; Gregory M Goldgof; Andrea L Cheung; Jennifer L Walker; Edgar Vigil; Kenneth E Allen; Yevgeniya Antonova-Koch; Carolyn W Slayman; Yo Suzuki; Jacob D Durrant

doi:10.1186/s13321-018-0261-3

Two inhibitors of yeast plasma membrane ATPase 1 (ScPma1p): toward the development of novel antifungal therapies

J Cheminform. 2018 Feb 20;10(1):6. doi: 10.1186/s13321-018-0261-3.

Authors

Affiliations

¹ Division of Host Pathogen Systems and Therapeutics, Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
² Department of Synthetic Biology and Bioenergy, J. Craig Venter Institute, La Jolla, CA, 92037, USA.
³ Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
⁴ Department of Genetics, Yale University School of Medicine, New Haven, CT, 06520, USA.
⁵ Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 15260, USA. durrantj@pitt.edu.

Abstract

Given that many antifungal medications are susceptible to evolved resistance, there is a need for novel drugs with unique mechanisms of action. Inhibiting the essential proton pump Pma1p, a P-type ATPase, is a potentially effective therapeutic approach that is orthogonal to existing treatments. We identify NSC11668 and hitachimycin as structurally distinct antifungals that inhibit yeast ScPma1p. These compounds provide new opportunities for drug discovery aimed at this important target.

Keywords: Antifungal; Computer modeling; Drug resistance; In vitro evolution; P-type ATPase; PMA1; Saccharomyces cerevisiae.

Abstract

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