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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1fq0

E.C. name2-dehydro-3-deoxy-phosphogluconate aldolase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 4.1.2.14
CSA Homologues of 1fq0There are 14 Homologs
CSA Entries With UniProtID P0A955
CSA Entries With EC Number 4.1.2.14
PDBe Entry 1fq0
PDBSum Entry 1fq0
MACiE Entry 1fq0

Literature Report

Introduction2-ket-3-deoxy-phosphogluconate (KDPG) aldolase is a Class I aldolase of the glycolytic pathway. It catalyses the reversible cleavage of KDPG into the three carbon units pyruvate and glyceraldehyde-3-phosphate. The enzymatic aldol reaction is highly efficient, regioselective and shows high facial stereoselectivity.
MechansimIn the aldol condensation direction, Glu45 acts as a general base towards the protonated Lys133 through a structurally conserved water molecule. This activates the lysine residue towards nucleophilic attack the the pyruvate carbonyl, which with concomitant protonation of the hydroxyl group from Glu45 results in the elimination of water and formation of an imine intermediate. Glu45 initiates tautomerisation through proton transfer with the eliminated water, forming a carbinolamine. The glyceraldehyde-3-phosphate is then attacked by this intermediate at its carbonyl functionality, with simultaneous protonation from Glu45. This residue then acts as a base towards a hydrolytic water which attacks the imine, and initiates the collapse of the tetrahedral intermediate, releasing the free Lys133, Glu45, KDPG and reforming the conserved water molecule.
Reaction

Catalytic Sites for 1fq0

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GluA4545macie:sideChainThe residue acts as a general base within a proton relay with a water molecule to deprotonate Lys133, and therefore activate the residue to act as a nucleophile towards the substrate carbonyl. It also acts as a general acid towards the eliminated water. Because of the distance between the most likely substrate binding position and the residue, it is thought that most of its acid/base interactions are mediated through a structurally conserved water molecule.
LysA133133macie:sideChainThe residue acts as a nucleophile towards the substrate carbonyl, forming a Schiff imine with elimination of water. This water then remains in the active site to facilitate proton relay between the substrate and Glu45. Its pKa is modified through electrostatic interaction with Arg49 and the general base Glu45 via a water molecule.
ArgA4949macie:sideChainThe close proximity of the residue's positively charged side chain to the catalytic nucleophile Lys133 influences the residue's pKa, increasing its acidity and so the interaction enhances Lys133 nucleophilic character.

Literature References

Notes:
Fullerton SW
Mechanism of the Class I KDPG aldolase.
Bioorg Med Chem 2006 14 3002-3010
PubMed: 16403639
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