Журнал генетических синдромов и генной терапии
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Science Vision 2020 on Sulfur Metabolism

KV Venkatachalam

Many intracellular compounds are sulfonated. The universal sulfonate donor is 3’-phosphoadenosine 5’-phosphosulfate (PAPS). In humans PAPS is synthesized from inorganic sulfate by PAPS synthase (PAPSS) in two steps. First inorganic sulfate combines with adenylate moiety of ATP to form 3’-AdenosinePhosphosulate (APS) by ATP sulfurylase activity of the PAPSS. This enzyme domain activity is one of unique ATP α-βphospho-anhydride bond splitting enzyme that is much similar to type I tRNA synthetases. Pyrophosphate which is one of the byproduct is cleaved into two inorganic phosphates by ubiquitous pyrophosphates. APS in the next step is phosphorylated at the 3’-OH by another molecule of ATP by APS kinase domain of the PAPSS. APS kinase is a β-γ phospho anhydride bond splitter of ATP that possess Walker motif such as GxxGxxK to form the phosphoryl for transfer reaction. Years ago I was the first to molecularly clone, express, dissect the domain activities of human PAPSS from fetal brain. Currently we are interested in the developmental roles of PAPSS during mice brain development and its clinical correlations. Deficiency of PAPSS2 isoform leads to Spondylo Epimetaphyseal Dysplasia (SEMD) in humans. Thus we are interested in the biochemistry, molecular biology and the clinical relevance of the oxidized form of the sulfur, PAPS the sulfuryl donor in human biology and development.