InterPro domain: IPR004516

This entry represents histidine-tRNA ligase (HisS or HisRS) and its paralogue, ATP phosphoribosyltransferase regulatory subunit (HisZ). Despite the significant sequential and structural similarity, HisRS and HisZ have different functions [ 1 ]. HisRS is a class IIa aminoacyl-tRNA synthetase (ligase), while HisZ is a regulatory subunit of the hetero-octameric ATP phosphoribosyl transferase that regulate reactions initiating histidine biosynthesis [ 2 , 3 ].

From the phylogenetic analysis, HisZ proteins form a monophyletic group that attaches outside the predominant bacterial HisRS clade [ 4 ]. HisZ are represented in a highly divergent set of bacteria (including an aquificale, cyanobacteria, firmicutes, and proteobacteria), but are missing from other bacteria, including mycrobacteria and certain proteobacteria [ 5 ]. It has been suggested that the absences of HisZ from bacteria are due to its loss during evolution [ 5 ].

1. Crystal structures of trypanosomal histidyl-tRNA synthetase illuminate differences between eukaryotic and prokaryotic homologs. J. Mol. Biol. 397, 481-94
2. Regulation of the hetero-octameric ATP phosphoribosyl transferase complex from Thermotoga maritima by a tRNA synthetase-like subunit. Mol. Microbiol. 55, 675-86
3. Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralog. J. Biol. Chem. 280, 34096-104
4. Proteobacterial histidine-biosynthetic pathways are paraphyletic. J. Mol. Evol. 50, 339-47