InterPro domain: IPR000150

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 ]. Proteins in this entry are mostly uncharacterised, though they form a distinct subgroup within the HAD superfamily. Members are found almost exclusively in bacteria and many species contain several paralogs, for example Escherichia coli contains a total of six proteins from this entry. Sequence similarities suggest that these enzymes are phosphatases which work on phosphorylated sugars.

This entry represents a family belonging to the HAD superfamily. It is named after E. coli Cof and is notable for the large number of paralogues in many species. Cof is a phosphatase that catalyzes the hydrolysis of HMP-PP (4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate) to HMP-P (4-amino-2-methyl-5-hydroxymethylpyrimidine phosphate) [ 2 ].

E. coli YbiV ( P75792 ) also belongs to this group and has been experimentally characterised [ 3 ]. This enzyme catalyzes the hydrolysis of sugar phosphate to sugar and inorganic phosphate. It has a wide substrate specificity, catalyzing the hydrolysis of ribose-5-phosphate and glucose-6-phosphate most efficiently, but it is not known if these are the real substrates in vivo. The protein appears to be a monomer that contains two domains, an alpha-beta hydrolase domain that forms a Rossman fold, and an alpha-beta domain. The active site is found in a negatively charged cavity found at the interface between the two domains.

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. A genetic screen for the identification of thiamin metabolic genes. J. Biol. Chem. 279, 43555-9
3. YbiV from Escherichia coli K12 is a HAD phosphatase. Proteins 58, 790-801