InterPro: IPR000634 Serine/threonine dehydratase, pyridoxal-phosphate-binding site

Pyridoxal phosphate is the active form of vitamin B6 (pyridoxine or pyridoxal). PLP is a versatile catalyst, acting as a coenzyme in a multitude of reactions, including decarboxylation, deamination and transamination [1, 2, 3]. PLP-dependent enzymes are primarily involved in the biosynthesis of amino acids and amino acid-derived metabolites, but they are also found in the biosynthetic pathways of amino sugars and in the synthesis or catabolism of neurotransmitters; pyridoxal phosphate can also inhibit DNA polymerases and several steroid receptors [4]. Inadequate levels of pyridoxal phosphate in the brain can cause neurological dysfunction, particularly epilepsy [5].

PLP enzymes exist in their resting state as a Schiff base, the aldehyde group of PLP forming a linkage with the epsilon-amino group of an active site lysine residue on the enzyme. The alpha-amino group of the substrate displaces the lysine epsilon-amino group, in the process forming a new aldimine with the substrate. This aldimine is the common central intermediate for all PLP-catalysed reactions, enzymatic and non-enzymatic [6].

Serine and threonine dehydratases [7, 8] are functionally and structurally related pyridoxal-phosphate dependent enzymes. L-serine dehydratase (EC:4.3.1.17) and D-serine dehydratase (EC:4.3.1.18) catalyse the dehydratation of L-serine (respectively D-serine) into ammonia and pyruvate. Threonine dehydratase (EC:4.3.1.19) (TDH) catalyses the dehydratation of threonine into alpha-ketobutarate and ammonia. In Escherichia coli and other microorganisms, two classes of TDH are known to exist. One is involved in the biosynthesis of isoleucine, the other in hydroxamino acid catabolism. Threonine synthase (EC:4.2.3.1) is also a pyridoxal-phosphate enzyme, it catalyses the transformation of homoserine-phosphate into threonine. It has been shown [9] that threonine synthase is distantly related to the serine/threonine dehydratases. In all these enzymes, the pyridoxal-phosphate group is attached to a lysine residue.