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Search The CSA
PDB ID
UNIPROT ID
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Catalytic Site Atlas

CSA LITERATURE entry for 1gtp

E.C. nameGTP cyclohydrolase I
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 3.5.4.16
CSA Homologues of 1gtpThere are 13 Homologs
CSA Entries With UniProtID P0A6T5
CSA Entries With EC Number 3.5.4.16
PDBe Entry 1gtp
PDBSum Entry 1gtp
MACiE Entry M0038

Literature Report

IntroductionGTP cyclohydrolase (EC 3.5.4.16) catalyses the complex reaction which converts GTP to dihydroneopterin triphosphate. This is the first step of a pathway, which in plants and micro-organisms leads to tetrahydrofolate production, and in animals leads to tetrahydrobiopterin production. Tetrahydrobiopterin is biologically important as it serves as a cofactor in the production of catecholamines and nitric oxide. Genetic defects in GTP cyclohydrolase can therefore lead to severe neurological disorders.
MechansimThe GTP cyclohydrolase catalytic domain shares a CATH classification (3.50.11.20) with aspartylglucosaminidase (E.C.3.5.1.26) chain B. The two enzymes do not share similar reaction mechanisms or catalytic residues however. Two proposed mechanisms exist which differ in the nature of the nucleophile, which opens the imidazole ring. The reaction is initiated by histidine 179, which acts as an acid and donates a proton to N7. The positively charged ring is now susceptible to nucleophilic attack at C8 by either a water molecule or the sulphur atom of cysteine 110, which is in a disulphide bond with cysteine 189. Histidine 112 protonates the bridging O of the furanose ring which leads to the opening of the furanose ring. Amadori rearrangement of this intermediate and proton abstraction by a base thought to be serine 135 leads to another intermediate. The last stage of the reaction, the closure of the pterin ring system is thought to be non-enzymatically catalysed either on the protein surface, or in solution.
Reaction

Catalytic Sites for 1gtp

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisA179180macie:sideChain
HisA112113macie:sideChain

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisB179180macie:sideChain
HisB112113macie:sideChain

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisC179180macie:sideChain
HisC112113macie:sideChain

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisD179180macie:sideChain
HisD112113macie:sideChain

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisE179180macie:sideChain
HisE112113macie:sideChain

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisF179180macie:sideChain
HisF112113macie:sideChain

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisG179180macie:sideChain
HisG112113macie:sideChain

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisH179180macie:sideChain
HisH112113macie:sideChain

Annotated By Reference To The Literature - Site 9 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisI179180macie:sideChain
HisI112113macie:sideChain

Annotated By Reference To The Literature - Site 10 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisJ179180macie:sideChain
HisJ112113macie:sideChain

Annotated By Reference To The Literature - Site 11 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisK179180macie:sideChain
HisK112113macie:sideChain

Annotated By Reference To The Literature - Site 12 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisL179180macie:sideChain
HisL112113macie:sideChain

Annotated By Reference To The Literature - Site 13 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisM179180macie:sideChain
HisM112113macie:sideChain

Annotated By Reference To The Literature - Site 14 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisN179180macie:sideChain
HisN112113macie:sideChain

Annotated By Reference To The Literature - Site 15 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisO179180macie:sideChain
HisO112113macie:sideChain

Annotated By Reference To The Literature - Site 16 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisP179180macie:sideChain
HisP112113macie:sideChain

Annotated By Reference To The Literature - Site 17 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisQ179180macie:sideChain
HisQ112113macie:sideChain

Annotated By Reference To The Literature - Site 18 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisR179180macie:sideChain
HisR112113macie:sideChain

Annotated By Reference To The Literature - Site 19 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisS179180macie:sideChain
HisS112113macie:sideChain

Annotated By Reference To The Literature - Site 20 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
HisT179180macie:sideChain
HisT112113macie:sideChain

Literature References

Notes:
Nar H
Atomic structure of GTP cyclohydrolase I.
Structure 1995 3 459-466
PubMed: 7663943
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