PTS Proteins

Protein Information

The tetrahydrobiopterin (BH4) cofactor is essential for hepatic hydroxylase, which is involved in phenylalanine degradation and catecholamine and serotonin biosynthesis. BH4 is also an essential and limiting cofactor for all types of nitric oxide synthase. BH4 deficiency results in hyperphenylalaninemia and monoamine neurotransmitter depletion and is most commonly due to autosomal recessive mutation in 6-pyruvoyltetrahydropterin synthase (PTPS), the second enzyme for BH4 biosynthesis. The active site of PTPS consists of the pterin-anchoring Glu A107 neighbored by two catalytic motifs: a Zn(II) binding site and an inter-subunit catalytic triad formed by Cys A42, Asp B88 and His B89. The active site of PTPS undergoes a Zn and Mg-dependent reaction that includes a triphosphate elimination, a stereospecific reduction and the oxidation of both side hydroxyl groups. The catalytic triad of PTPS is involved in the deprotonation of the side-chain carbons of substrates. In addition, Ser 19 of human PTPS may be a substrate for cGMP-dependent protein kinase type II phosphorylation in vivo, which is essential for normal activity of PTPS.

Synonyms

6-pyruvoyl tetrahydrobiopterin synthase; 6-pyruvoyltetrahydropterin synthase; 6-pyruvoyl-tetrahydropterin synthase; PTP synthase; PTPS; Pts