DB code: S00270

CATH domain 3.30.479.10 : Tetrahydropterin Synthase; Chain A Catalytic domain
E.C. 4.2.3.12
CSA 1b66
M-CSA 1b66
MACiE M0084

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P27213 6-pyruvoyl tetrahydrobiopterin synthase
PTP synthase
PTPS
EC 4.2.3.12
NP_058916.1 (Protein)
NM_017220.1 (DNA/RNA sequence)
PF01242 (PTPS)
[Graphical View]

KEGG enzyme name
6-pyruvoyltetrahydropterin synthase
2-amino-4-oxo-6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydroxypteridine triphosphate lyase
6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterintriphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P27213 PTPS_RAT 7,8-dihydroneopterin 3''-triphosphate = 6- pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate. Homohexamer formed of two homotrimers in a head to head fashion. Binds 1 zinc ion per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00790 Folate biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C00305 C04895 C03684 C00536
E.C.
Compound Zinc Magnesium 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin 6-pyruvoyl-5,6,7,8-tetrahydropterin Triphosphate
Type heavy metal divalent metal (Ca2+, Mg2+) amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate phosphate group/phosphate ion
ChEBI 29105
 29105
 		18420
 18420
 		18372
 18372
 		17804
 17804
 		39949
 39949
PubChem 32051
 32051
 		888
 888
 		121885
 121885
 		128973
 128973
 		983
 983
1b66A Bound:_ZN Unbound Unbound Analogue:BIO Unbound
1b66B Bound:_ZN Unbound Unbound Analogue:BIO Unbound
1b6zA Bound:_ZN Unbound Unbound Unbound Unbound
1b6zB Bound:_ZN Unbound Unbound Unbound Unbound
1gtqA Bound:_ZN Unbound Unbound Unbound Unbound
1gtqB Bound:_ZN Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1b66,1b6z,1gtq & Swiss-prot;P27213

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b66A CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)
1b66B CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)
1b6zA CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)
1b6zB CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)
1gtqA CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)
1gtqB CYS 42;HIS 89;GLU 133 HIS 23;HIS 48;HIS 50(Zinc binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme 1 4
[2]
p.1259-1261
[3]
Fig.8, Fig.9, p.361-362, p.364-365 4
[5]
Fig.7, p.855-857 4

References
[1]
Resource
Comments
Medline ID
PubMed ID 2406138
Journal Eur J Biochem
Year 1990
Volume 187
Pages 651-6
Authors Ghisla S, Kuster T, Steinerstauch P, Leimbacher W, Richter WJ, Raschdorf F, Dahinden R, Curtius HC
Title 1H-NMR and mass spectrometric studies of tetrahydropterins. Evidence for the structure of 6-pyruvoyl tetrahydropterin, an intermediate in the biosynthesis of tetrahydrobiopterin.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 94185630
PubMed ID 8137809
Journal EMBO J
Year 1994
Volume 13
Pages 1255-62
Authors Nar H, Huber R, Heizmann CW, Thony B, Burgisser D
Title Three-dimensional structure of 6-pyruvoyl tetrahydropterin synthase, an enzyme involved in tetrahydrobiopterin biosynthesis.
Related PDB 1gtq
Related UniProtKB P27213
[3]
Resource
Comments
Medline ID
PubMed ID 7563095
Journal J Mol Biol
Year 1995
Volume 253
Pages 358-69
Authors Burgisser DM, Thony B, Redweik U, Hess D, Heizmann CW, Huber R, Nar H
Title 6-Pyruvoyl tetrahydropterin synthase, an enzyme with a novel type of active site involving both zinc binding and an intersubunit catalytic triad motif; site-directed mutagenesis of the proposed active center, characterization of the metal binding site and modelling of substrate binding.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9774432
Journal J Biol Chem
Year 1998
Volume 273
Pages 28132-41
Authors Bracher A, Eisenreich W, Schramek N, Ritz H, Gotze E, Herrmann A, Gutlich M, Bacher A
Title Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 99150429
PubMed ID 10024455
Journal J Mol Biol
Year 1999
Volume 286
Pages 851-60
Authors Ploom T, Thony B, Yim J, Lee S, Nar H, Leimbacher W, Richardson J, Huber R, Auerbach G
Title Crystallographic and kinetic investigations on the mechanism of 6-pyruvoyl tetrahydropterin synthase.
Related PDB 1b66 1b6z
Related UniProtKB P27213
[6]
Resource
Comments
Medline ID
PubMed ID 10737935
Journal Proteins
Year 2000
Volume 39
Pages 142-54
Authors Colloc'h N, Poupon A, Mornon JP
Title Sequence and structural features of the T-fold, an original tunnelling building unit.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12123838
Journal FEBS Lett
Year 2002
Volume 523
Pages 234-8
Authors Woo HJ, Hwang YK, Kim YJ, Kang JY, Choi YK, Kim CG, Park YS
Title Escherichia coli 6-pyruvoyltetrahydropterin synthase ortholog encoded by ygcM has a new catalytic activity for conversion of sepiapterin to 7,8-dihydropterin.
Related PDB
Related UniProtKB

Comments
E.C. number was transferred from 4.6.1.10 to 4.2.3.12.

Created Updated
2004-06-28 2009-02-26