Journal article
Crystal structures of Trypanosoma brucei hypoxanthine – guanine – xanthine phosphoribosyltransferase in complex with IMP, GMP and XMP
D Terán, E Doleželová, DT Keough, D Hocková, A Zíková, LW Guddat
FEBS Journal | WILEY | Published : 2019
DOI: 10.1111/febs.14987
Abstract
The 6-oxopurine phosphoribosyltransferases (PRTs) are drug targets for the treatment of parasitic diseases. This is due to the fact that parasites are auxotrophic for the 6-oxopurine bases relying on salvage enzymes for the synthesis of their 6-oxopurine nucleoside monophosphates. In Trypanosoma brucei, the parasite that is the aetiological agent for sleeping sickness, there are three 6-oxopurine PRT isoforms. Two are specific for hypoxanthine and guanine, whilst the third, characterized here, uses all three naturally occurring bases with similar efficiency. Here, we have determined crystal structures for TbrHGXPRT in complex with GMP, XMP and IMP to investigate the structural basis for subs..
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Awarded by European Research Council
Funding Acknowledgements
The initial crystallographic conditions were determined using the Mosquito and Rock Imager facilities at the University of Queensland Remote-Operation Crystallization and X-ray Diffraction facility (UQROCX). The views expressed here are those of the authors and not necessarily those of the Australian Synchrotron. This work was supported by NHMRC (Grant No. 1147368), the Institute of Organic Chemistry and Biochemistry (RVO 61388963), the Czech Science Foundation (Grant No. 19-07707S) and the ERC CZ LL1205 ERD Funds (No. CZ. 02.1.01/0.0/0.0/16_019/0000759). Scholarship funding to DT was by the Ecuadorian Government through the SENESCYT.