Background
PAPS Synthase 1 and 2 are bifunctional enzymes with both ATP sulfurylase and APS kinase activity. They mediate two reactions to generate 3'-phosphoadenosine-5'-phosphosulfate, a critical intermediate in the sulfate activation pathway. PAPS is the sulfate donor co-substrate for all sulfotransferase enzymes and is required to catalyze the sulfate conjugation of many endogenous and exogenous compounds. For example, PAPSS1 and PAPSS2 are responsible for catalyzing the sulfation of steroid hormones, which increases their water solubility and reduces their biological activity, suggesting modulation of PAPS synthases as a possible avenue for treatment of hormone-dependent cancers. Inhibition of PAPSS1 was also shown to increase the sensitivity of some cancer cell lines to DNA-damage agents both in vitro and in vivo, suggesting further potential utility for PAPS synthase inhibitors in cancer therapy.
References
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