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

The large HAD (haloacid dehalogenase) superfamily of hydrolases comprises P -type ATPases, phosphatases, epoxide hydrolases and L-2-haloacid dehalogena ses. A comparison of the three-dimensional structure of L-2-haloacid dehalo genase with that of the response regulator protein CheY allowed the assignm ent of a conserved pair of aspartate residues as the Mg2+-binding site in t he P-type ATPase and phosphatase members of the superfamily, From the resul ting model of the active site, a conserved serine/threonine residue is sugg ested to be involved in phosphate binding, and a mechanism comprising a pho sphoaspartate intermediate is postulated.