Nucleotide preference is defined by a histidine residue. (A) Excerpt from a multiple sequence alignment of 440 nucleotidyltransferase sequences. After the alignment sequences were grouped into phylogenetic subgroups and two representative sequences are depicted. Sequence similarities within each group were color-coded. Confirmed nucleotidyltransferases Cid1, TUT4, TUT6, and TUT7 and their homologs contain a histidine (#), which confers uridyl selectivity. Adenylyltransferases either substitute histidine with a smaller amino acid (leucine in Papd1) or entirely lack this residue (Gld2). (B) Excerpt of a structural alignment between Cid1 (pdb 4FHP) and Papd1 (pdb 3PQ1). The depicted ribbon diagram shows a structural superposition of human mitochondrial Papd1 (gray) and Cid1 (cyan). Asn367 of Cid1 aligns with the homologous Asn273 of Papd1. Cid1 His336 points into the active site and makes contact with UTP.
