6-pyruvoyl tetrahydrobiopterin synthase; PTP synthase (PTPS, PTS)

Function

• role in the biosynthesis of tetrahydrobiopterin
• catalyzes transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin
• cofactor biosynthesis; tetrahydrobiopterin biosynthesis
• tetrahydrobiopterin from 2-amino-4-hydroxy-6-(erythro-1,2,3- trihydroxypropyl)-dihydropteridine triphosphate: step 1/3
• phosphorylation of Ser-19 is required for maximal enzyme activity

7,8-dihydroneopterin 3'-triphosphate
          <-->
6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate

Cofactor: binds 1 Zn+2 per subunit (putative)

Kinetic parameters:

• KM=8.1 uM for 7,8-dihydroneopterin triphosphate
• Vmax=120 nmol/min/mg enzyme

Structure

• homohexamer formed of two homotrimers in a head to head fashion
• belongs to the PTPS family
• the active site is at the interface between 2 subunits
• the proton acceptor Cys is on one subunit, & the charge relay system is on the other subunit

Pathology

• defects in PTS are a cause of hyperphenylalaninemia

More general terms

• synthase
• phosphoprotein

Database

• UniProt: http://www.uniprot.org/uniprot/Q03393.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5805
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5805
• OMIM: https://mirror.omim.org/entry/261640