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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1ald

E.C. namefructose-bisphosphate aldolase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz) 4.1.2.13
CSA Homologues of 1aldThere are 42 Homologs
CSA Entries With UniProtID P04075
CSA Entries With EC Number 4.1.2.13
PDBe Entry 1ald
PDBSum Entry 1ald
MACiE Entry 1ald

Literature Report

IntroductionFructose-1,6-bisphosphate muscle aldolase is an essential glycolytic enzyme that catalyses reversible carbon-carbon bond formation by cleaving fructose 1,6-bisphosphate (FBP) to yield dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P), or in the other direction the condensation of DHAP and G3P to form FBP.
MechansimA conserved lysine residue attacks the carbonyl carbon of G3P in a nucleophilic addition. Several proton transfers occur leading to elimination of water and a double bond rearrangement of the bound intermediate, resulting in formation of the Schiff base. More proton transfers and double bond rearrangements promote interconversion of the iminium and enamine forms of the bound intermediate. Binding of DHAP leads to the condensation reaction between the bound intermediate and DHAP. More proton transfers and addition of water to the intermediate result in elimination of the linear form of FBP, leaving the lysine residue. Further proton transfers catalyse the ring closure of FBP as well as returning the enzyme to its original state.
Assignment of the role of charged active site residues is complex as these residues can mediate proton transfers by general acid/base catalysis, stabilise or destabilise charges, and because of their proximity to each other are susceptible to electrostatic modification of their pKa charges.
Reaction

Catalytic Sites for 1ald

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
AspA3334macie:sideChainAs well as substrate binding and positioning, the negative charge of Asp33 is important for promoting the charged form of Lys146, ensuring stabilisation of intermediates and efficient proton transfers.
LysA146147macie:sideChainThe charged form of Lys146 stabilises negative charges in the substrate and intermediates, and encourages the negatively charged form of Tyr363.
GluA187188macie:sideChainInvolved in several key proton transfers.
GluA189190macie:sideChainActivates a water molecule.
LysA229230macie:sideChainForms Schiff base with G3P.
SerA300301macie:sideChainStabilises enamine intermediate.
TyrA363364macie:sideChainStereospecifically removes the C3 pro-S proton from the substrate.

Literature References

Notes:Though the mechanisms of proton transfer etc. shown on MACiE are currently believed to be correct, they may well be revised in light of computational studies in the future.
Littlechild JA
A data-based reaction mechanism for type I fructose bisphosphate aldolase.
Trends Biochem Sci 1993 18 36-39
PubMed: 8488556
St-Jean M
Stereospecific proton transfer by a mobile catalyst in mammalian fructose-1,6-bisphosphate aldolase.
J Biol Chem 2007 282 31028-31037
PubMed: 17728250
St-Jean M
Charge stabilization and entropy reduction of central lysine residues in fructose-bisphosphate aldolase.
Biochemistry 2009 48 4528-4537
PubMed: 19354220
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