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MetaCyc Enzyme: GTP cyclohydrolase III

Gene: arfA Accession Numbers: G-11167 (MetaCyc), MJ0145

Synonyms: gch3

Species: Methanocaldococcus jannaschii

Subunit composition of GTP cyclohydrolase III = [ArfA]4
         GTP cyclohydrolase III monomer = ArfA

Summary:
Four classes of GTP cyclohydrolases are currrently known:

GTP cyclohydrolase I converts GTP to 7,8-dihydroneopterin 3'-triphosphate, the first step in the biosynthesis of folate.

GTP cyclohydrolase II converts GTP to 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one, the first step in the bacterial and eukaryotic pathways for flavin biosynthesis.

GTP cyclohydrolase III converts GTP to 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one, the first step in the archaeal pathways for flavin biosynthesis.

GTP cyclohydrolase IV converts GTP to 7,8-dihydroneopterin 2',3'-cyclic phosphate, an early intermediate to pterins in archaea.

About This Enzyme

Flavin biosynthesis in the hyperthermophilic euryarchaeon Methanocaldococcus jannaschii starts with the conversion of GTP to 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one, catalyzed by GTP cyclohydrolase III. Unlike the case of GTP cyclohydrolase II, where this compoind is an intermediate that is processed further by elimination of formate, it is the final product for this enzyme.

While GTP cyclohydrolase II hydrolyzes the α-β phosphate anhydride bond of GTP, this enzyme completely hydrolyzes pyrophosphate to inorganic phosphate, resulting in a much faster steady-state turnover rate [Graham02]. The enzyme requires Mg2+ and is stimulated by large cations such as K+ or NH4+.

The enzyme has been crystalized, and the crystal structure was solved at 2 Å [Morrison08a]. The structure revealed that the enzyme is a tetramer of identical subunits, composed of two dimers. It also showed the presence of three metal atoms at the active site - two Mg2+, and one likely to be K+, which is involved in substrate recognition [Morrison08a].

Molecular Weight of Polypeptide: 30.286 kD (from nucleotide sequence), 37.0 kD (experimental) [Graham02 ]

Molecular Weight of Multimer: 98.3 kD (experimental) [Graham02]

Unification Links: Entrez-gene:1450989 , Protein Model Portal:Q57609 , SMR:Q57609 , String:243232.MJ0145 , UniProt:Q57609

Relationship Links: InterPro:IN-FAMILY:IPR007839 , PDB:Structure:2QV6 , Pfam:IN-FAMILY:PF05165 , ProDom:IN-FAMILY:PD313320

Gene-Reaction Schematic: ?

Credits:
Created 18-Mar-2009 by Caspi R , SRI International


Enzymatic reaction of: GTP cyclohydrolase

EC Number: 3.5.4.29

GTP + 3 H2O <=> 2-amino-5-formylamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one + 2 phosphate + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for GTP: dGTP [Graham02 ]

In Pathways: flavin biosynthesis II (archaea)

Cofactors or Prosthetic Groups: Mg2+ [Graham02]

Activators (Allosteric): K+ [Graham02] , ammonium [Graham02]

Inhibitors (Unknown Mechanism): Li+ [Graham02]

Kinetic Parameters:

Substrate
Km (μM)
Citations
GTP
54.0
[Graham02]

T(opt): 70 °C [Graham02]

pH(opt): 8-9 [Graham02]


References

Graham02: Graham DE, Xu H, White RH (2002). "A member of a new class of GTP cyclohydrolases produces formylaminopyrimidine nucleotide monophosphates." Biochemistry 41(50);15074-84. PMID: 12475257

Morrison08a: Morrison SD, Roberts SA, Zegeer AM, Montfort WR, Bandarian V (2008). "A new use for a familiar fold: the X-ray crystal structure of GTP-bound GTP cyclohydrolase III from Methanocaldococcus jannaschii reveals a two metal ion catalytic mechanism." Biochemistry 47(1);230-42. PMID: 18052207


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Nov 27, 2014, biocyc14.