Histidine Triad ( HIT ) Superfamily

Abstract

Histidine triad (HIT) enzymes are an ancient superfamily of nucleotide hydrolases and transferases that catalyse mechanistically similar but biologically distinct reactions on nucleotide‐containing substrates in pathways important for cellular growth, apoptosis and deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and carbohydrate metabolism. Four branches of HIT enzymes function as nucleotide hydrolases. These enzymes include homologues and paralogues of histidine triad nucleotide‐binding (Hint) protein, fragile histidine triad (Fhit) protein, Aprataxin and scavenger decapping protein (Dcps). One diverse branch of the HIT superfamily contains nucleotide transferases and phosphorylases related to galactose‐1‐phosphate uridylyltransferase (GalT), AppppA phosphorylase, adenylylsulfate:phosphate adenylyltransferase (APAT), adenosine diphosphate (ADP)‐glucose phosphorylase, and Vtc2, the guanosine diphosphate (GDP)‐ l ‐galactose phosphorylase. This review provides tools to discern the identities and the probable functions of new HIT enzymes from their sequences.

Histidine-Triad Hydrolases Provide Resistance to Peptide-Nucleotide Antibiotics

“…2A). An additional gene, mccH, is located 89 downstream of the mccB 1 gene and encodes a protein belonging to a histidine triad (HIT) 90 superfamily (12). We next attempted to reconstruct the production of each of the H. minutum compounds in a heterologous E. coli host.…”

“…HinT Eco (19), and its human homologue, hHint1 (20, 21). The characteristic feature of the HIT 188 superfamily proteins is a conserved histidine triad motif, HxHxHxx, where H is a histidine, and x 189 are hydrophobic residues (12). The three essential catalytic histidines form a network of 190 hydrogen bonds with the substrate that promote proton transfer from protonated C-terminal 191 histidine of the triad (H103 in HinT Eco or H102 in HinT Hmi The loss of functional activity by MccH Hmi mutant K103H suggested that this residue, specific to 227…”