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Overview for MACiE Entry M0222

Version history

General Information

EC Number: 4.1.2.13 (A member of the Lyases, Carbon-carbon lyases, Aldehyde-lyases)

Enzyme Name: fructose-bisphosphate aldolase (Class I)

Biological Species: Oryctolagus cuniculus (Rabbit)

Catalytic Chain UniprotKB Accession Codes:

  • P00883 - Fructose-bisphosphate aldolase A

Representative PDB Code: 2qut - DIHYDROXYACETONE PHOSPHATE ENAMINE INTERMEDIATE IN FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE FROM RABBIT MUSCLE (Resolution = 1.88 Å).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of D-glyceraldehyde 3- phosphate

Image of glycerone phosphate

right arrow

Image of D-fructose 1,6-bisphosphate

D-glyceraldehyde 3- phosphate
C00118
CHEBI:59776
glycerone phosphate
C00111
CHEBI:57642
D-fructose 1,6-bisphosphate
C00354
CHEBI:49299

Overall Comment: In Archea, Tyr146 acts as the proton donor catalysing the conversion between the cabinolamine and the Schiff base and in Eukarya this proton donor is Glu187 [4]. There are 3 isoforms of this enzyme: A (found in muscle, prefers fructose-1,6-bisphosphate over fructose-1-phosphate as a substrate), B (found in liver, has no substrate preference) and C (found in brain and shows bisphosphate preference).


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Stepwise Description of the Reaction

Step 1Lys229 attacks the carbonyl carbon of D-glyceraldehyde 3- phosphate in a nucleophilic addition.
Step 2The oxyanion formed deprotonates the bound Lys229.
Step 3Lys229 initiates an elimination of water, which gains an extra proton from Glu187.
Step 4The phosphate of the bound intermediate deprotonates water, which in turn deprotonates Tyr363.
Step 5Tyr363 deprotonates the C1-H of the bound intermediate, initiating a double bond rearrangement that leaves Lys229 with a lone pair of electrons.
Step 6Glu187 deprotonates water, which deprotonates a second water which deprotonates the phosphate of the bound intermediate.
Step 7Glycerone phosphate binds, displacing one of the water molecules. Lys229 initiates a nucleophilic addition of the bound intermediate to the glycerone phosphate. The formed oxyanion deprotonates Glu187.
Step 8Glu187 deprotonates water, which attacks the imine carbon of the covalenlty bound intermediate in a nucleophilic addition.
Step 9Lys229 deprotonates the formed hydroxyl group, which initiates an elimination of the linear form of D-fructose 1,6-bisphosphate and neutral Lys229.
Step 10Phosphate deprotonates hydroxyl, and the carbonyl oxygen re-protonates from Lys229, which in turn re-protonates from the phosphate, thus catalysing the ring closure of D-fructose 1,6-bisphosphate.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Lys 146 A Side Chain
Ser 300 A Side Chain
Tyr 363 A Side Chain
Asp 33 A Side Chain
Lys 229 A Side Chain
Glu 187 A Side Chain
Glu 189 A Side Chain

References

  1. J. A. Littlechild et al. (1993), Trends Biochem. Sci., 18, 36-39. A data-based reaction mechanism for type I fructose bisphosphate aldolase.
    Medline: 8488556
  2. M. St-Jean et al. (2007), J. Biol. Chem., 282, 31028-31037. Stereospecific proton transfer by a mobile catalyst in mammalian fructose-1,6-bisphosphate aldolase.
    Medline: 17728250
  3. M. St-Jean et al. (2005), J. Biol. Chem., 280, 27262-27270. High resolution reaction intermediates of rabbit muscle fructose-1,6-bisphosphate aldolase: substrate cleavage and induced fit.
    Medline: 15870069
  4. E. Lorentzen et al. (2005), Biochemistry, 44, 4222-4229. Mechanism of the Schiff base forming fructose-1,6-bisphosphate aldolase: structural analysis of reaction intermediates.
    Medline: 15766250

Homologue information for M0222 (2qut)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with the same EC number (different mechanisms):

MACiE Entry Enzyme Name PDB code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0052 fructose-bisphosphate aldolase (Class II) 1b57 0.3172 0.2454 Compare

Compare of the other reactions in MACiE with EC number 4.1.2.13


Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0102 L-lactate dehydrogenase (cytochrome)
1.1.2.3
1fcb 3.20.20.70
0.10510.1575Compare
M0108 2,4-dienoyl-CoA reductase (NADPH)
1.3.1.34
1ps9 3.20.20.70
0.24390.2200Compare
M0109 dihydroorotate oxidase
1.3.3.1
1d3g 3.20.20.70
0.19020.2329Compare
M0111 glutamate synthase (ferredoxin)
1.4.7.1
1ofd 3.20.20.70
0.57380.2133Compare
M0114 trimethylamine dehydrogenase
1.5.8.2
2tmd 3.20.20.70
0.13670.0830Compare
M0319 NADPH dehydrogenase
1.6.99.1
1oya 3.20.20.70
0.13080.0529Compare
M0148 transaldolase
2.2.1.2
1onr 3.20.20.70
0.92810.4762Compare
M0008 nicotinate-nucleotide diphosphorylase (carboxylating)
2.4.2.19
1qpr 3.20.20.70
0.16340.4681Compare
M0243 pyridoxine 5'-phosphate synthase
2.6.99.2
1ho1 3.20.20.70
0.72520.1454Compare
M0050 orotidine-5'-phosphate decarboxylase
4.1.1.23
1dbt 3.20.20.70
0.04120.2999Compare
M0252 indole-3-glycerol-phosphate synthase
4.1.1.48
1igs 3.20.20.70
0.32330.675Compare
M0236 3-dehydro-L-gulonate-6-phosphate decarboxylase
4.1.1.85
1q6l 3.20.20.70
0.12870.4649Compare
M0052 fructose-bisphosphate aldolase (Class II)
4.1.2.13
1b57 3.20.20.70
0.31720.2454Compare
M0054 3-dehydroquinate dehydratase (type I)
4.2.1.10
1qfe 3.20.20.70
0.46950.3764Compare
M0230 porphobilinogen synthase
4.2.1.24
1gzg 3.20.20.70
0.64170.3432Compare
M0267 dihydrodipicolinate synthase
4.2.1.52
1dhp 3.20.20.70
0.28690.2669Compare
M0270 ribulose-phosphate 3-epimerase
5.1.3.1
1h1z 3.20.20.70
0.16050.2243Compare
M0324 triosephosphate isomerase
5.3.1.1
1tph 3.20.20.70
0.15610.45Compare
M0223 pyruvate carboxylase
6.4.1.1
2qf7 3.20.20.70
0.27910.3096Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.20.20.70


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

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catalytic activity (molecular function)
fructose-bisphosphate aldolase activity (molecular function)
protein binding (molecular function)
glycolytic process (biological process)
metabolic process (biological process)
lyase activity (molecular function)
protein homotetramerization (biological process)
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