3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1)

3'-phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) is a bifunctional enzyme critical for generating the universal sulfate donor, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), in metazoans. It catalyzes two sequential reactions: first, the ATP sulfurylase domain combines ATP and inorganic sulfate to form adenosine 5'-phosphosulfate (APS); second, the APS kinase domain phosphorylates APS to yield PAPS. PAPS is then utilized by all cellular sulfotransferases for the modification of hormones, drugs, components of the extracellular matrix, and other biomolecules. PAPSS1 is expressed in multiple tissues, including testis, pancreas, kidney, liver, and endothelial cells, and is required for normal biosynthesis of sulfated L-selectin ligands. Genetic defects in related sulfate activation pathways are associated with skeletal and metabolic disorders, although PAPSS2 is more closely tied to known pathologies. No targeted therapies against PAPSS1 are currently available, but any pharmacologic intervention would carry risks related to impaired sulfation metabolism.

Other names

Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1Sulfate adenylyltransferaseAdenylyl-sulfate kinasePAPS synthase 1SK1SATATP-sulfurylaseSulfate adenylate transferase3'-phosphoadenosine-5'-phosphosulfate synthaseAPS kinaseAdenosine-5'-phosphosulfate 3'-phosphotransferaseAdenylylsulfate 3'-phosphotransferaseSulfurylase kinase 1

Not applicable (as no approved drugs directly target PAPSS1). In principle, inhibitors would block PAPS synthesis and impair cellular sulfation capacity, affecting downstream sulfotransferases.