Crystallization and preliminary X-ray diffraction study of the farnesyl diphosphate synthase from Trypanosoma brucei

Acta Crystallographica. Section D, Biological Crystallography
Junhong MaoE Oldfield

Abstract

Farnesyl diphosphate synthase (FPPS) catalyses the formation of farnesyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate and is an RNAi-validated drug target in Trypanosoma brucei, the causative agent of African sleeping sickness. A T. brucei FPPS (390 amino acids) has been expressed in Escherichia coli and the recombinant protein has been crystallized in the absence and presence of the bisphosphonate inhibitor minodronate. Diffraction data were collected at 100 K using synchrotron radiation from both crystal types. Crystals obtained in the absence of minodronate belong to space group I222, with unit-cell parameters a = 61.43, b = 118.12, c = 120.04 A, while crystals grown in the presence of minodronate belong to space group C2, with unit-cell parameters a = 131.98, b = 118.10, c = 63.25 A, beta = 112.48 degrees. An initial model of the drug-free protein has been built using a homology model with the molecular-replacement method and refined to 3.3 A resolution. It shows mostly helical structure and resembles the structure of avian farnesyl diphosphate synthase, but with the addition of two loop regions.

Citations

Mar 25, 2009·Journal of the American Chemical Society·Yonghui ZhangEric Oldfield
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yi-Liang LiuEric Oldfield
Jan 20, 2016·Expert Opinion on Drug Discovery·Juan B RodriguezSergio H Szajnman
Apr 15, 2008·Experimental Parasitology·Marcela FerellaRoberto Docampo
Jul 14, 2007·Insect Biochemistry and Molecular Biology·Stephanie E SenGregory Roberts
Aug 8, 2006·ChemMedChem·Jean-Michel RondeauWolfgang Jahnke
Jun 17, 2020·Chembiochem : a European Journal of Chemical Biology·Lena MünzkerWolfgang Jahnke

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