Towards an understanding of the functional significance of N-terminal domain divergence in human AMP deaminase isoforms

Abstract

Human AMP deaminase (AMPD; EC 3.5.4.6) isoforms are encoded by a multigene family and have conserved C-terminal domains that contain catalytic residues and an ATP-binding site. N-terminal domains diverge dramatically, yet are conserved when compared across mammalian species. Cross-species conservation of entire gene-specific polypeptides (e.g., rat versus human AMPD1) suggests that divergent N-terminal domains may play a role in isoform-specific properties of the enzyme. It now has become evident that the majority of published data used to characterize purified AMPD isoforms were likely derived from preparations lacking significant portions of their N-terminal domains (up to nearly 100 residues). Accumulating evidence indicates that divergent N-terminal sequences do influence catalytic behavior, protein-protein interactions, and intracellular distributions of this enzyme.