A superfamily of metalloenzymes unifies phosphopentomutase and cofactor-independent phosphoglycerate mutase with alkaline phosphatases and sulfatases

Sequence analysis of the probable archaeal phosphoglycerate mutase resulted in the identification of a superfamily of metalloenzymes with similar meta l-binding sites and predicted conserved structural fold. This superfamily u nites alkaline phosphatase, N-acetylgalactosamine-4-sulfatase, and cerebros ide sulfatase, enzymes with known three-dimensional structures, with phosph opentomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase, phosphoglycerol transferase, phosphonate monoesterase, streptomycin-6-phosp hate phosphatase, alkaline phosphodiesterase/nucleotide pyrophosphatase PC- 1, and several closely related sulfatases. In addition to the metal-binding motifs, all these enzymes contain a set of conserved amino acid residues t hat are likely to be required for the enzymatic activity. Mutational change s in the vicinity of these residues in several sulfatases cause mucopolysac charidosis (Hunter, Maroteaux-Lamy, Morquio, and Sanfilippo syndromes) and metachromatic leucodystrophy.