Structural domains comprising this superfamily share the structure of phosphoribosyl-AMP cyclohydrolase (PR-AMP), product of hisI gene which catalyses the first step in histidine biosynthesis. This metabolic pathway is of great interest from an evolutionary point of view due to the diversity of gene organizations and protein structures. One example of such diversity comes from the HisI gene, which can exist alone or as a fusion with hisE.

The structure of the HisI catalytic site is consistent with a reaction mechanism similar to those of nucleoside deaminases and both Zn2+ and Mg2+ are both key players in the catalytic mechanism PMID:16042384.