PROSITE documentation PDOC52114

ATP-dependent vitamin kinase domain profile

The ATP-dependent vitamin kinase family belongs to the ribokinase superfamily, which are transferases that catalyze the phosphorylation of a primary alcohol group on small aromatic molecules or carbohydrates. Unlike the members of the other two families (ribokinase and ADP-dependent family), its members lack a small domain that functions as the active site lid in the other families. Moreover, members of the ATP-dependent vitamin kinase show diverse activities as this family includes hydroxymethylpyrimidine kinases (HMPK, EC 2.7.1.49), phosphomethylpyrimidine kinase activity (HMPPK, EC 2.7.4.7), pyridoxal kinases (PLK, EC 2.7.1.35) and hydroxyethylthiazole kinases (THZK, EC 2.7.1.50), enzymes that participate in the biosynthesis de novo of active (phosphorylated) forms of vitamin B1 (thiamine pyrophosphate) and B6 (PLP) in bacteria, essential cofactors for several enzymes involved in the metabolism of amino acids and carbohydrates. Although at first sight it seems that these enzymes can be easily split in different groups based on their substrate specificities, the fact is that several members of this protein family are able to phosphorylate more than one substrate. Several bifunctional enzymes that phosphorylate hydroxymethylpyrimidine (HMP) and pyridoxal (PL) have been described besides enzymes specific towards HMP. The HMPK group can be divided into specific HMPKs and bifunctional HMPK/PLKs whereas the PLK group includes enzymes from prokaryotes (pdxY and pdxK) and eukaryotes. The PLK activity present in the current bifunctional enzymes must have appeared in a convergent event independently of the PLK activity of pdxY and pdxK genes [1,2,3].

The family of ATP-dependent vitamin kinases from the ribokinase superfamily features a single domain with a conserved Rossmann-like fold, thus structurally diverging from other enzymes of this superfamily that have, in addition, a small domain composed of a β-sheet that may also include some α-helical insertions. The structure is formed by a single large domain, composed of a central β-sheet of eight parallel strands surrounded by eight helices, arranged three and five on each side of the sheet (see <PDB:7L07>). Regions of highly dynamic loops could adopt ordered conformations upon substrate binding events, as reported for other members of the family. The active site is located in a cavity between the central β-sheet and the α-helices. A conserved basic residue (Cys or Asp) in the active site deprotonates the hydroxyl group of the phosphate acceptor, making a direct nucleophilic attack on the γ-phosphate of ATP in an in-line displacement mechanism [1,2,3].

The profile we developed covers the entire ATP-dependent vitamin kinase domain.