Cloning and characterization of the cDNA encoding human adenylosuccinate synthetase

Abstract

Adenylosuccinate synthetase (AS) catalyzes the first committed step in the conversion of IMP to AMP. A cDNA was isolated from a human liver library which encodes a protein of 455 amino acids (Mr of 49.925). Alignments of human, mouse, Dictyostelium discoideum and E. coli AS sequences identify a number of invariant residues which are likely to be important for structure and/or catalysis. The human AS sequence was also 19% identical to the human urea cycle enzyme, arginosuccinate synthetase (ASS), which catalyses a chemically similar reaction. Both human liver and HcLa AS mRNA showed signals of 2.3 and 2.8 kb. An unmodified N-terminus is required for function of the human AS enzyme in E. coli mutants lacking the bacterial enzyme. The human cDNA provides a means to assess the possible role of AS abnormalities in unclassified, idiopathic cases of gout.