InterPro domain: IPR036412

The haloacid dehydrogenase (HAD) superfamily includes phosphatases, phosphonatases, P-type ATPases, beta-phosphoglucomutases, phosphomannomutases, and dehalogenases, which are involved in a variety of cellular processes ranging from amino acid biosynthesis to detoxification[ 1 ].

Crystal structures of proteins from the HAD superfamily show that these proteins all share a conserved alpha/beta-domain classified as a hydrolase fold, which is similar to the Rossmann fold [ 2 ]. This conserved domain usually contains an insertion (sub)domain. For example, the crystal structure of a phosphoglycolate phosphatase from Thermoplasma acidophilum [ 3 ] revealed two distinct domains, a larger core domain and a smaller cap domain. The large domain is composed of a centrally located five-stranded parallel beta-sheet with strand order S10, S9, S8, S1, S2 and a small beta-hairpin, strands S3 and S4. This central sheet is flanked by a set of three alpha-helices on one side and two helices on the other. The topology of the large domain is conserved; however, structural variation is observed in the smaller domain among the different functional classes of the haloacid dehalogenase superfamily.

The large HAD-like superfamily of hydrolases comprises P-type ATPases, phosphatases, epoxide hydrolases and L-2-haloacid dehalogenases [ 3 ].

1. Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search. J. Mol. Biol. 244, 125-32
2. Structure- and function-based characterization of a new phosphoglycolate phosphatase from Thermoplasma acidophilum. J. Biol. Chem. 279, 517-26
3. Identification of the Mg2+-binding site in the P-type ATPase and phosphatase members of the HAD (haloacid dehalogenase) superfamily by structural similarity to the response regulator protein CheY. Biochem. J. 339 ( Pt 2), 223-6