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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1eyi

E.C. namefructose-bisphosphatase
SpeciesSus scrofa (Pig)
E.C. Number (IntEnz) 3.1.3.11
CSA Homologues of 1eyiThere are 80 Homologs
CSA Entries With UniProtID P00636
CSA Entries With EC Number 3.1.3.11
PDBe Entry 1eyi
PDBSum Entry 1eyi
MACiE Entry 1eyi

Literature Report

IntroductionFructose 1,6-bis-phosphate (FBPase) hydrolyses fructose 1,6-bis-phosphate to fructose 6-phosphate and phosphate. The enzyme plays a crucial role in gluconeogenesis, the formation of glucose from non-carbohydrate carbon containing substrates. The enzyme is only capable of catalysing the forward reaction, while phosphofructokinase catalyses the reverse reaction. Regulation of the two enzyme is performed by metabolites such as fructose 2,6 bis-phosphate, ensuring that enhances reactivity of one enzyme is accompanied by suppressed reactivity of the other.
MechansimThere are two divalent metal cations present within the catalytic site. Mg(2+) at site one is directly coordinated to the 1-(OH) of the 6 fructose phosphate product as a fifth coordinating ligand. The cation is thought to stabilise the negative charge of the hydroxide group before the transfer of a proton from Asp68, which relays a proton from the substrate neutralises the product. The second metal coordinates to a nucleophilic water molecule, also polarised through hydrogen bonds to Asp74 and Glu98, which abstracts a proton from a second coordinated water. The resulting hydroxide ion is the attacking nucleophile, displacing the 6 fructose phosphate in an Sn2 mechanism. The resulting oxide is protonated as stated above.
Reaction

Catalytic Sites for 1eyi

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA7475macie:sideChainThe residue's anionic carboxylic side chain hydrogen bonds to the basic water molecule in the close proximity Mg(2+) coordination sphere. The resulting polarisation enhances the basic character of the water molecule, activating it towards deprotonating a second, adjacent water molecule.
GluA9899macie:sideChainThe residue's anionic carboxylic side chain hydrogen bonds to the basic water molecule in the close proximity Mg(2+) coordination sphere. The resulting polarisation enhances the basic character of the water molecule, activating it towards deprotonating a second, adjacent water molecule.
AspA6869macie:sideChainThe residue acts as a proton carrier from the substrate to the product. It initially forms a hydrogen bond with the proton of the 1-phosphate group, and after the SN2 displacement step has taken place, relays the proton to the anionic 6-fructose phosphate intermediate.

Literature References

Notes:
Choe JY
Crystal structures of fructose 1,6-bisphosphatase: mechanism of catalysis and allosteric inhibition revealed in product complexes.
Biochemistry 2000 39 8565-8574
PubMed: 10913263
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