|Gene:||arfA||Accession Numbers: G-11167 (MetaCyc), MJ0145|
Species: Methanocaldococcus jannaschii
Subunit composition of
GTP cyclohydrolase III = [ArfA]4
GTP cyclohydrolase III monomer = ArfA
Four classes of GTP cyclohydrolases are currrently known:
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.
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 [Graham02a]. 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 [Morrison08]. 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 [Morrison08].
Molecular Weight of Polypeptide: 30.286 kD (from nucleotide sequence), 37.0 kD (experimental) [Graham02a ]
Molecular Weight of Multimer: 98.3 kD (experimental) [Graham02a]
Enzymatic reaction of: GTP cyclohydrolase
EC Number: 188.8.131.52
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.
In Pathways: flavin biosynthesis II (archaea)
T(opt): 70 °C [Graham02a]
pH(opt): 8-9 [Graham02a]
Morrison08: 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
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