text: TET enzymes are dioxygenases in the family of alpha-ketoglutarate-dependent hydroxylases.  A TET enzyme is an alpha-ketoglutarate (α-KG) dependent dioxygenase that catalyses an oxidation reaction by incorporating a single oxygen atom from molecular oxygen (O) into its substrate, 5-methylcytosine in DNA (5mC), to produce the product 5-hydroxymethylcytosine in DNA.  This conversion is coupled with the oxidation of the co-substrate α-KG to succinate and carbon dioxide (see Figure).
  The first step involves the binding of α-KG and 5-methylcytosine to the TET enzyme active site.  The TET enzymes each harbor a core catalytic domain with a double-stranded β-helix fold that contains the crucial metal-binding residues found in the family of Fe(II)/α-KG- dependent oxygenases.  α-KG coordinates as a bidentate ligand (connected at two points) to Fe(II) (see Figure), while the 5mC is held by a noncovalent force in close proximity. The TET active site contains a highly conserved triad motif, in which the catalytically-essential Fe(II) is held by two histidine residues and one aspartic acid residue (see Figure).  The triad binds to one face of the Fe center, leaving three labile sites available for binding α-KG and O (see Figure).  TET then acts to convert 5-methylcytosine to 5-hydroxymethylcytosine while α-ketoglutarate is converted to succinate and CO.