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- W4296127109 endingPage "2105" @default.
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- W4296127109 abstract "Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, affects over 8 million people worldwide. Current antiparasitic treatments for Chagas disease are ineffective in treating advanced, chronic stages of the disease, and are noted for their toxicity. Like most parasitic protozoa, T. cruzi is unable to synthesize purines de novo, and relies on the salvage of preformed purines from the host. Hypoxanthine–guanine phosphoribosyltransferases (HGPRTs) are enzymes that are critical for the salvage of preformed purines, catalyzing the formation of inosine monophosphate (IMP) and guanosine monophosphate (GMP) from the nucleobases hypoxanthine and guanine, respectively. Due to the central role of HGPRTs in purine salvage, these enzymes are promising targets for the development of new treatment methods for Chagas disease. In this study, we characterized two gene products in the T. cruzi CL Brener strain that encodes enzymes with functionally identical HGPRT activities in vitro: TcA (TcCLB.509693.70) and TcC (TcCLB.506457.30). The TcC isozyme was kinetically characterized to reveal mechanistic details on catalysis, including identification of the rate-limiting step(s) of catalysis. Furthermore, we identified and characterized inhibitors of T. cruzi HGPRTs originally developed as transition-state analogue inhibitors (TSAIs) of Plasmodium falciparum hypoxanthine–guanine–xanthine phosphoribosyltransferase (PfHGXPRT), where the most potent compound bound to T. cruzi HGPRT with low nanomolar affinity. Our results validated the repurposing of TSAIs to serve as selective inhibitors for orthologous molecular targets, where primary and secondary structures as well as putatively common chemical mechanisms are conserved." @default.
- W4296127109 created "2022-09-17" @default.
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- W4296127109 date "2022-09-15" @default.
- W4296127109 modified "2023-10-11" @default.
- W4296127109 title "Kinetic Characterization and Inhibition of <i>Trypanosoma cruzi</i> Hypoxanthine–Guanine Phosphoribosyltransferases" @default.
- W4296127109 cites W1486489268 @default.
- W4296127109 cites W1563650227 @default.
- W4296127109 cites W192686486 @default.
- W4296127109 cites W1964193450 @default.
- W4296127109 cites W1964803671 @default.
- W4296127109 cites W1970327093 @default.
- W4296127109 cites W1973649308 @default.
- W4296127109 cites W1975055427 @default.
- W4296127109 cites W1978232724 @default.
- W4296127109 cites W1979606430 @default.
- W4296127109 cites W1984252886 @default.
- W4296127109 cites W1984416760 @default.
- W4296127109 cites W1987519639 @default.
- W4296127109 cites W1994659943 @default.
- W4296127109 cites W1997986150 @default.
- W4296127109 cites W1998920561 @default.
- W4296127109 cites W1999179917 @default.
- W4296127109 cites W2004080823 @default.
- W4296127109 cites W2010204713 @default.
- W4296127109 cites W2010786471 @default.
- W4296127109 cites W2011668781 @default.
- W4296127109 cites W2016175830 @default.
- W4296127109 cites W2019562067 @default.
- W4296127109 cites W2021217831 @default.
- W4296127109 cites W2023033821 @default.
- W4296127109 cites W2023436525 @default.
- W4296127109 cites W2024017407 @default.
- W4296127109 cites W2031386057 @default.
- W4296127109 cites W2031573500 @default.
- W4296127109 cites W2031640770 @default.
- W4296127109 cites W2037960835 @default.
- W4296127109 cites W2038146608 @default.
- W4296127109 cites W2040349186 @default.
- W4296127109 cites W2052440430 @default.
- W4296127109 cites W2056999054 @default.
- W4296127109 cites W2057327466 @default.
- W4296127109 cites W2057882821 @default.
- W4296127109 cites W2061464257 @default.
- W4296127109 cites W2062762024 @default.
- W4296127109 cites W2072621169 @default.
- W4296127109 cites W2073815262 @default.
- W4296127109 cites W2074631079 @default.
- W4296127109 cites W2076728845 @default.
- W4296127109 cites W2081190990 @default.
- W4296127109 cites W2082361461 @default.
- W4296127109 cites W2085266415 @default.
- W4296127109 cites W2090696875 @default.
- W4296127109 cites W2091077160 @default.
- W4296127109 cites W2107925176 @default.
- W4296127109 cites W2132251081 @default.
- W4296127109 cites W2139717699 @default.
- W4296127109 cites W2140078415 @default.
- W4296127109 cites W2142570120 @default.
- W4296127109 cites W2145440636 @default.
- W4296127109 cites W2147830249 @default.
- W4296127109 cites W2149976637 @default.
- W4296127109 cites W2152974563 @default.
- W4296127109 cites W2155159495 @default.
- W4296127109 cites W2162778646 @default.
- W4296127109 cites W2287219098 @default.
- W4296127109 cites W2322471444 @default.
- W4296127109 cites W2769983079 @default.
- W4296127109 cites W2792476365 @default.
- W4296127109 cites W2793816505 @default.
- W4296127109 cites W2805210705 @default.
- W4296127109 cites W2888322168 @default.
- W4296127109 cites W2899523040 @default.
- W4296127109 cites W2904851802 @default.
- W4296127109 cites W2939453559 @default.
- W4296127109 cites W2950329712 @default.
- W4296127109 cites W2964234501 @default.
- W4296127109 cites W2997410299 @default.
- W4296127109 cites W3001566363 @default.
- W4296127109 cites W3011727225 @default.
- W4296127109 cites W3092654498 @default.
- W4296127109 cites W3139306982 @default.
- W4296127109 cites W4225753912 @default.
- W4296127109 cites W4231307075 @default.
- W4296127109 cites W4235938477 @default.
- W4296127109 cites W4301020220 @default.
- W4296127109 cites W4378951057 @default.
- W4296127109 cites W953150473 @default.