PDBsum entry 1gtq

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protein metals links
Tetrahydrobiopterin biosynthesis PDB id
Protein chains
138 a.a. *
_ZN ×2
Waters ×240
* Residue conservation analysis
PDB id:
Name: Tetrahydrobiopterin biosynthesis
Title: 6-pyruvoyl tetrahydropterin synthase
Structure: 6-pyruvoyl tetrahydropterin synthase. Chain: a, b. Engineered: yes
Source: Rattus rattus. Black rat. Organism_taxid: 10117. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Trimer (from PQS)
2.30Å     R-factor:   0.204    
Authors: H.Nar,R.Huber,C.W.Heizmann,B.Thoeny,D.Buergisser
Key ref: H.Nar et al. (1994). Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an enzyme involved in tetrahydrobiopterin biosynthesis. EMBO J, 13, 1255-1262. PubMed id: 8137809
16-Sep-95     Release date:   03-Apr-96    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P27213  (PTPS_RAT) -  6-pyruvoyl tetrahydrobiopterin synthase
144 a.a.
138 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 6-pyruvoyltetrahydropterin synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Biopterin Biosynthesis
      Reaction: 7,8-dihydroneopterin 3'-triphosphate = 6-pyruvoyl-5,6,7,8- tetrahydropterin + triphosphate
7,8-dihydroneopterin 3'-triphosphate
= 6-pyruvoyl-5,6,7,8- tetrahydropterin
+ triphosphate
      Cofactor: Magnesium
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cellular_component   3 terms 
  Biological process     tetrahydrobiopterin biosynthetic process   1 term 
  Biochemical function     lyase activity     5 terms  


    Added reference    
EMBO J 13:1255-1262 (1994)
PubMed id: 8137809  
Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an enzyme involved in tetrahydrobiopterin biosynthesis.
H.Nar, R.Huber, C.W.Heizmann, B.Thöny, D.Bürgisser.
The crystal structure of rat liver 6-pyruvoyl tetrahydropterin synthase has been solved by multiple isomorphous replacement and refined to a crystallographic R-factor of 20.4% at 2.3 A resolution. 6-Pyruvoyl tetrahydrobiopterin synthase catalyses the conversion of dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, the second of three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP. The functional enzyme is a hexamer of identical subunits. The 6-pyruvoyl tetrahydropterin synthase monomer folds into a sequential, four-stranded, antiparallel beta-sheet with a 25 residue, helix-containing insertion between strands 1 and 2 at the bottom of the molecule, and a segment between strands 2 and 3 forming a pair of antiparallel helices, layered on one side of the beta-sheet. Three 6-pyruvoyl tetrahydropterin synthase monomers form an unusual 12-stranded antiparallel beta-barrel by tight association between the N- and C-terminal beta-strands of two adjacent subunits. The barrel encloses a highly basic pore of 6-12 A diameter. Two trimers associate in a head-to-head fashion to form the active enzyme complex. The substrate-binding site is located close to the trimer-trimer interface and comprises residues from three monomers: A, A' and B. A metal-binding site in the substrate-binding pocket is formed by the three histidine residues 23, 48 and 50 from one 6-pyruvoyl tetrahydropterin synthase subunit. Close to the metal, but apparently not liganding it, are residues Cys42, Glu133 (both from A) and His89 (from B), which might serve as proton donors and acceptors during catalysis.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  18931427 J.E.Spoonamore, S.A.Roberts, A.Heroux, and V.Bandarian (2008).
Structure of a 6-pyruvoyltetrahydropterin synthase homolog from Streptomyces coelicolor.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 875-879.
PDB code: 3d7j
  18271114 K.H.Seo, Supangat, H.L.Kim, Y.S.Park, C.O.Jeon, and K.H.Lee (2008).
Purification, crystallization and preliminary crystallographic analysis of a 6-pyruvoyltetrahydropterin synthase homologue from Esherichia coli.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 105-107.  
  17183164 B.Bagautdinov, M.Sugahara, and N.Kunishima (2007).
Purification, crystallization and preliminary crystallographic analysis of archaeal 6-pyruvoyl tetrahydrobiopterin synthase homologue PH0634 from Pyrococcus horikoshii OT3.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 15-17.  
15767583 S.G.Van Lanen, J.S.Reader, M.A.Swairjo, Crécy-Lagard, B.Lee, and D.Iwata-Reuyl (2005).
From cyclohydrolase to oxidoreductase: discovery of nitrile reductase activity in a common fold.
  Proc Natl Acad Sci U S A, 102, 4264-4269.  
11087827 G.Auerbach, A.Herrmann, A.Bracher, G.Bader, M.Gutlich, M.Fischer, M.Neukamm, M.Garrido-Franco, J.Richardson, H.Nar, R.Huber, and A.Bacher (2000).
Zinc plays a key role in human and bacterial GTP cyclohydrolase I.
  Proc Natl Acad Sci U S A, 97, 13567-13572.
PDB codes: 1fb1 1fbx
10874306 N.Blau, T.Scherer-Oppliger, A.Baumer, M.Riegel, A.Matasovic, A.Schinzel, J.Jaeken, and B.Thöny (2000).
Isolated central form of tetrahydrobiopterin deficiency associated with hemizygosity on chromosome 11q and a mutant allele of PTPS.
  Hum Mutat, 16, 54-60.  
10737935 N.Colloc'h, A.Poupon, and J.P.Mornon (2000).
Sequence and structural features of the T-fold, an original tunnelling building unit.
  Proteins, 39, 142-154.  
10765502 S.Laufs, S.H.Kim, S.Kim, N.Blau, and B.Thöny (2000).
Reconstitution of a metabolic pathway with triple-cistronic IRES-containing retroviral vectors for correction of tetrahydrobiopterin deficiency.
  J Gene Med, 2, 22-31.  
10378270 T.Ploom, C.Haussmann, P.Hof, S.Steinbacher, A.Bacher, J.Richardson, and R.Huber (1999).
Crystal structure of 7,8-dihydroneopterin triphosphate epimerase.
  Structure, 7, 509-516.
PDB code: 1b9l
9774432 A.Bracher, W.Eisenreich, N.Schramek, H.Ritz, E.Götze, A.Herrmann, M.Gütlich, and A.Bacher (1998).
Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.
  J Biol Chem, 273, 28132-28141.  
9586996 M.Hennig, A.D'Arcy, I.C.Hampele, M.G.Page, C.Oefner, and G.E.Dale (1998).
Crystal structure and reaction mechanism of 7,8-dihydroneopterin aldolase from Staphylococcus aureus.
  Nat Struct Biol, 5, 357-362.
PDB codes: 1dhn 2dhn
9450907 T.T.Liu, K.J.Hsiao, S.F.Lu, S.J.Wu, K.F.Wu, S.H.Chiang, X.Q.Liu, R.G.Chen, and W.M.Yu (1998).
Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.
  Hum Mutat, 11, 76-83.  
9222755 B.Thöny, and N.Blau (1997).
Mutations in the GTP cyclohydrolase I and 6-pyruvoyl-tetrahydropterin synthase genes.
  Hum Mutat, 10, 11-20.  
9182560 C.Ahn, J.Byun, and J.Yim (1997).
Purification, cloning, and functional expression of dihydroneopterin triphosphate 2'-epimerase from Escherichia coli.
  J Biol Chem, 272, 15323-15328.  
9266180 E.Gouaux (1997).
Channel-forming toxins: tales of transformation.
  Curr Opin Struct Biol, 7, 566-573.  
9405351 G.Auerbach, A.Herrmann, M.Gütlich, M.Fischer, U.Jacob, A.Bacher, and R.Huber (1997).
The 1.25 A crystal structure of sepiapterin reductase reveals its binding mode to pterins and brain neurotransmitters.
  EMBO J, 16, 7219-7230.
PDB codes: 1nas 1oaa 1sep
9360612 N.Colloc'h, M.el Hajji, B.Bachet, G.L'Hermite, M.Schiltz, T.Prangé, B.Castro, and J.P.Mornon (1997).
Crystal structure of the protein drug urate oxidase-inhibitor complex at 2.05 A resolution.
  Nat Struct Biol, 4, 947-952.
PDB code: 1uox
9222757 T.Oppliger, B.Thöny, C.Kluge, A.Matasovic, C.W.Heizmann, A.Ponzone, M.Spada, and N.Blau (1997).
Identification of mutations causing 6-pyruvoyl-tetrahydropterin synthase deficiency in four Italian families.
  Hum Mutat, 10, 25-35.  
8841415 C.Kluge, L.Brecevic, C.W.Heizmann, N.Blau, and B.Thöny (1996).
Chromosomal localization, genomic structure and characterization of the human gene and a retropseudogene for 6-pyruvoyltetrahydropterin synthase.
  Eur J Biochem, 240, 477-484.  
  8897596 J.D.Cronk, J.A.Endrizzi, and T.Alber (1996).
High-resolution structures of the bifunctional enzyme and transcriptional coactivator DCoH and its complex with a product analogue.
  Protein Sci, 5, 1963-1972.
PDB codes: 1dco 1dcp
  8846895 N.Kim, J.Kim, D.Park, C.Rosen, D.Dorsett, and J.Yim (1996).
Structure and expression of wild-type and suppressible alleles of the Drosophila purple gene.
  Genetics, 142, 1157-1168.  
8618856 H.Nar, R.Huber, G.Auerbach, M.Fischer, C.Hösl, H.Ritz, A.Bracher, W.Meining, S.Eberhardt, and A.Bacher (1995).
Active site topology and reaction mechanism of GTP cyclohydrolase I.
  Proc Natl Acad Sci U S A, 92, 12120-12125.  
  7744010 R.Ficner, U.H.Sauer, G.Stier, and D.Suck (1995).
Three-dimensional structure of the bifunctional protein PCD/DCoH, a cytoplasmic enzyme interacting with transcription factor HNF1.
  EMBO J, 14, 2034-2042.  
7493990 T.Oppliger, B.Thöny, H.Nar, D.Bürgisser, R.Huber, C.W.Heizmann, and N.Blau (1995).
Structural and functional consequences of mutations in 6-pyruvoyltetrahydropterin synthase causing hyperphenylalaninemia in humans. Phosphorylation is a requirement for in vivo activity.
  J Biol Chem, 270, 29498-29506.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.