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Plasmodium Gametocyte Inhibition Identified from a Natural-Product-Based Fragment Library.
Title | Plasmodium Gametocyte Inhibition Identified from a Natural-Product-Based Fragment Library. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Vu, H, Roullier, C, Campitelli, M, Trenholme, KR, Gardiner, DL, Andrews, KT, Skinner-Adams, T, Crowther, GJ, Van Voorhis, WC, Quinn, RJ |
Journal | ACS Chem Biol |
Date Published | 2013 Oct 3 |
ISSN | 1554-8937 |
Abstract | Fragment-based screening is commonly used to identify compounds with relatively weak but efficient localized binding to protein surfaces. We used mass spectrometry to study fragment-sized three-dimensional natural products. We identified seven securinine-related compounds binding to Plasmodium falciparum 2'-deoxyuridine 5'-triphosphate nucleotidohydrolase (PfdUTPase). Securinine bound allosterically to PfdUTPase, enhancing enzyme activity and inhibiting viability of both P. falciparum gametocyte (sexual) and blood (asexual) stage parasites. Our results provide a new insight into mechanisms that may be applicable to transmission-blocking agents. |
DOI | 10.1021/cb400582b |
Alternate Journal | ACS Chem. Biol. |
PubMed ID | 24079418 |