Get   for     ? 
 Site search     ? 
Catalytic Site Atlas Version 2.2.12
Find Annotated Site: PDB code:
Swiss-Prot code:
EC number:
Help
CSA entry for 1ok4
Original Entry
Title:
Lyase
Compound:
Fructose-bisphosphate aldolase class i
Mutant:
No
UniProt/Swiss-Prot:
P58315-ALF1_THETE
EC Class:
4.1.2.13
Other CSA Entries:
Overview of all sites for 1ok4
Homologues of 1ok4
Entries for UniProt/Swiss-Prot: P58315
Entries for EC: 4.1.2.13
Other Databases:
PDB entry: 1ok4
PDBsum entry: 1ok4
UniProt/Swiss-Prot: P58315
IntEnz entry: 4.1.2.13
Literature Report:
Introduction:
Fructose-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.
Mechanism:
The 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.
Sites:

Click to Display Catalytic Site (Get help with this section)
Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
ASPA 24 24Sidechain
Acid/baseSubstrate
Acts as a general acid/base catalyst.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11705376 Related protein: UniProt P00883 Conservation of residue
PubMed ID 12941964 Current protein Conservation of residue
PubMed ID 12941964 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11705376 Related protein: UniProt P00883 Residue is positioned appropriately (ligand position known)
PubMed ID 12941964 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11705376 Related protein: UniProt P00883 Residue is covalently bound to intermediate, based on structural data

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
TYRA 146 146Sidechain
Acid/baseWater
Acid/baseSubstrate
Acts as a general acid/base catalyst - can activate water in the either direction for nucleophilic attack.
Evidence from paper Evidence concerns Evidence type
PubMed ID 12941964 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 11705376 Related protein: UniProt P00883 Conservation of residue
PubMed ID 12941964 Current protein Conservation of residue
PubMed ID 11705376 Related protein: UniProt P00883 Residue is positioned appropriately (ligand position known)
PubMed ID 12941964 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11705376 Related protein: UniProt P00883 Residue is covalently bound to intermediate, based on structural data

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 177 177Sidechain
Acid/baseSubstrate
NucleophileSubstrate
Acts as the nucleophile in formation of the Schiff-base and activates the substrate and facilitates loss of the intermediate through general acid/base catalysis.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11705376 Related protein: UniProt P00883 Residue is positioned appropriately (ligand position known)
PubMed ID 11705376 Related protein: UniProt P00883 Residue is covalently bound to intermediate, based on structural data
PubMed ID 12941964 Current protein Structural similarity to homologue of known mechanism
PubMed ID 12941964 Current protein Residue is positioned appropriately (ligand position known)
PubMed ID 12941964 Current protein Conservation of residue
PubMed ID 11705376 Related protein: UniProt P00883 Conservation of residue
Notes:
This enzyme can exist in many high-oligomer bioactive forms.
References:
1
Crystal structure of an archaeal class I aldolase and the evolution of (betaalpha)8 barrel proteins.
E. Lorentzen and E. Pohl and P. Zwart and A. Stark and R. B. Russell and T. Knura and R. Hensel and B. Siebers
J Biol Chem 278, (47) 47253-60, (2003).
12941964
2
Snapshots of catalysis: the structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate.
K. H. Choi and J. Shi and C. E. Hopkins and D. R. Tolan and K. N. Allen
Biochemistry 40, (46) 13868-75, (2001).
11705376
Which EBI biological databases are available and how do I access them? EBI Site Map