PTPS Human

6-Pyruvoyltetrahydropterin Synthase (PTPS) is a crucial enzyme in the biosynthesis of tetrahydrobiopterin (BH4), a cofactor essential for the activity of several enzymes, including those involved in the synthesis of neurotransmitters like serotonin and nitric oxide . The recombinant form of this enzyme is produced using human gene sequences expressed in bacterial systems like E. coli .

PTPS catalyzes the second step in the biosynthesis of tetrahydrobiopterin from guanosine triphosphate (GTP). Specifically, it converts 7,8-dihydroneopterin triphosphate to 6-pyruvoyltetrahydropterin by eliminating an inorganic triphosphate group . This reaction is irreversible and critical for the proper functioning of the biosynthetic pathway .

PTPS is a hexameric enzyme composed of identical subunits, forming a structure with D3 symmetry . Each subunit contains a 12-stranded antiparallel β-barrel, creating a pore within the enzyme. The active site, where the catalytic reaction occurs, is located at the interface of the subunits and involves several key residues, including histidines and a zinc ion .

The enzyme is encoded by the PTS gene, which is located on chromosome 11 in humans . Mutations in the PTS gene can lead to disorders such as hyperphenylalaninemia and tetrahydrobiopterin deficiency, which can result in severe neurological symptoms .

Recombinant human PTPS is typically produced in E. coli systems. The recombinant protein often includes an N-terminal His-tag to facilitate purification . The protein is expressed, harvested, and purified using conventional chromatography techniques to achieve high purity levels .

Mutations in the PTS gene can lead to a deficiency in tetrahydrobiopterin, resulting in metabolic disorders that affect neurotransmitter synthesis. These conditions can be severe and require early diagnosis and treatment to manage symptoms effectively .