spacer
View the latest EBI news stories and important announcements...
more

spacer
Search The CSA
PDB ID
UNIPROT ID
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1ok4

E.C. namefructose-bisphosphate aldolase
SpeciesThermoproteus tenax ()
E.C. Number (IntEnz) 4.1.2.13
CSA Homologues of 1ok4There are 13 Homologs
CSA Entries With UniProtID P58315
CSA Entries With EC Number 4.1.2.13
PDBe Entry 1ok4
PDBSum Entry 1ok4
MACiE Entry 1ok4

Literature Report

IntroductionFructose-1,6-bisphosphate aldolase participates in two major metabolic pathways. In gluconeogenesis it catalyses the aldol condensation of a ketose, dihydroxyacetone phosphate (DHAP) and an aldose, glyceraldehyde 3-phosphate (G3P) to form the acylic form of fructose 1,6-bisphosphate (FBP). In glycolysis, they catalyse the reverse cleavage reaction. The aldol condensation is a key reaction in synthetic chemistry that aldolases catalyse with control of stereochemistry.
Aldolases belong to class I or class II, depending on the reaction mechanism. This annotation refers to class II aldolases, which are alpha/beta(8) barrel structures. The class II enzymes are not found in mammals, and have an absolute requirement for a divalent cation, usually Zn. However a recently discovered archaeal fructose-1,6-bisphosphate aldolase belongs to a third class of aldolase.
MechansimThe catalytic mechanism of archaic fructose-1,6-bisphosphate aldolase proceeds after binding and ring-opening of the substrate. Lys 177 attacks the C2-carbonyl carbon nucleophilically to form a carbinolamine using general acid catalysis as well. General acid catalysis by Tyr 146 allows dehydration to form the imine or hydrolysis in the reverse direction - the C2 hydroxyl is protonated to leave as water to leave the Schiff-base or deprotonated for attack of the imine in the reverse. Proton abstraction by Asp 24 leads to C3-C4 bond cleavage to release glucose 3-phosphate and leave a carbanion/enamine which is protonated by Asp 24 to form the product imine. Tyr 146 activates a water for nucleophilic attack by general base catalysis which is followed by general base catalysis by Lys 177 to regenerate the active site and give release of dihydroxyacetone phosphate.
Reaction

Catalytic Sites for 1ok4

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA2424macie:sideChainActs as a general acid/base catalyst.
LysA177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrA146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspB2424macie:sideChainActs as a general acid/base catalyst.
LysB177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrB146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 3 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspC2424macie:sideChainActs as a general acid/base catalyst.
LysC177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrC146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 4 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspD2424macie:sideChainActs as a general acid/base catalyst.
LysD177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrD146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 5 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspE2424macie:sideChainActs as a general acid/base catalyst.
LysE177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrE146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 6 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspF2424macie:sideChainActs as a general acid/base catalyst.
LysF177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrF146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 7 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspG2424macie:sideChainActs as a general acid/base catalyst.
LysG177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrG146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 8 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspH2424macie:sideChainActs as a general acid/base catalyst.
LysH177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrH146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 9 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspI2424macie:sideChainActs as a general acid/base catalyst.
LysI177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrI146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Annotated By Reference To The Literature - Site 10 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspJ2424macie:sideChainActs as a general acid/base catalyst.
LysJ177177macie:sideChainActs as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
TyrJ146146macie:sideChainActs as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.

Literature References

Notes:This enzyme can exist in many high-oligomer bioactive forms.
Lorentzen E
Crystal structure of an archaeal class I aldolase and the evolution of (betaalpha)8 barrel proteins.
J Biol Chem 2003 278 47253-47260
PubMed: 12941964
Choi KH
Snapshots of catalysis: the structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate.
Biochemistry 2001 40 13868-13875
PubMed: 11705376
spacer
spacer