DB code: S00199

RLCP classification 6.10.400600.113 : Double-bonded atom exchange
5.121.671000.6111 : Elimination
8.112.3600000.6580 : Isomerization
6.20.7800.6111 : Double-bonded atom exchange
CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 4.1.2.13
CSA 1ald
M-CSA 1ald
MACiE

CATH domain Related DB codes (homologues)
3.20.20.70 : TIM Barrel S00215 S00217 S00218 S00219 S00532 S00198 S00220 S00745 S00537 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00200 S00201 S00221 S00222 S00847 S00224 S00225 S00226 D00014 D00029 M00141 T00015 T00239 D00664 D00665 D00804 D00863 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04075 Fructose-bisphosphate aldolase A
EC 4.1.2.13
Muscle-type aldolase
Lung cancer antigen NY-LU-1
NP_000025.1 (Protein)
NM_000034.3 (DNA/RNA sequence)
NP_001121089.1 (Protein)
NM_001127617.2 (DNA/RNA sequence)
NP_001230106.1 (Protein)
NM_001243177.1 (DNA/RNA sequence)
NP_908930.1 (Protein)
NM_184041.2 (DNA/RNA sequence)
NP_908932.1 (Protein)
NM_184043.2 (DNA/RNA sequence)
PF00274 (Glycolytic)
[Graphical View]
P05062 Fructose-bisphosphate aldolase B
EC 4.1.2.13
Liver-type aldolase
NP_000026.2 (Protein)
NM_000035.3 (DNA/RNA sequence)
PF00274 (Glycolytic)
[Graphical View]
P00883 Fructose-bisphosphate aldolase A
EC 4.1.2.13
Muscle-type aldolase
NP_001075707.1 (Protein)
NM_001082238.1 (DNA/RNA sequence)
PF00274 (Glycolytic)
[Graphical View]
P07764 Fructose-bisphosphate aldolase
EC 4.1.2.13
NP_001262985.1 (Protein)
NM_001276056.1 (DNA/RNA sequence)
NP_524515.2 (Protein)
NM_079791.4 (DNA/RNA sequence)
NP_733140.2 (Protein)
NM_170261.2 (DNA/RNA sequence)
NP_733141.1 (Protein)
NM_170262.2 (DNA/RNA sequence)
NP_733142.1 (Protein)
NM_170263.3 (DNA/RNA sequence)
NP_733143.1 (Protein)
NM_170264.2 (DNA/RNA sequence)
NP_733144.3 (Protein)
NM_170265.3 (DNA/RNA sequence)
NP_733145.3 (Protein)
NM_170266.3 (DNA/RNA sequence)
NP_996300.1 (Protein)
NM_206577.2 (DNA/RNA sequence)
PF00274 (Glycolytic)
[Graphical View]
P14223 Fructose-bisphosphate aldolase
EC 4.1.2.13
41 kDa antigen
PF00274 (Glycolytic)
[Graphical View]
P07752 Fructose-bisphosphate aldolase, glycosomal
EC 4.1.2.13
PF00274 (Glycolytic)
[Graphical View]

KEGG enzyme name
fructose-bisphosphate aldolase
aldolase
fructose-1,6-bisphosphate triosephosphate-lyase
fructose diphosphate aldolase
diphosphofructose aldolase
fructose 1,6-diphosphate aldolase
ketose 1-phosphate aldolase
phosphofructoaldolase
zymohexase
fructoaldolase
fructose 1-phosphate aldolase
fructose 1-monophosphate aldolase
1,6-Diphosphofructose aldolase
SMALDO
D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04075 ALDOA_HUMAN D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Homotetramer.
P05062 ALDOB_HUMAN D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Homotetramer.
P00883 ALDOA_RABIT D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Tetramer.
P07764 ALF_DROME D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Homotetramer.
P14223 ALF_PLAFA D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Homotetramer.
P07752 ALF_TRYBB D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Glycosome.

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis
MAP00030 Pentose phosphate pathway
MAP00051 Fructose and mannose metabolism
MAP00710 Carbon fixation in photosynthetic organisms

Compound table
Substrates Products Intermediates
KEGG-id C00354 C00111 C00118
E.C. (post-bond-cleavage)
Compound D-Fructose 1,6-bisphosphate Glycerone phosphate D-Glyceraldehyde 3-phosphate Intermediate
Type carbohydrate,phosphate group/phosphate ion carbohydrate,phosphate group/phosphate ion carbohydrate,phosphate group/phosphate ion
ChEBI 37736
 37736
 		16108
 16108
 		29052
 29052
PubChem 172313
 172313
 		668
 668
 		439168
 439168
1a5cA Unbound Unbound Unbound Unbound
1a5cB Unbound Unbound Unbound Unbound
1adoA Unbound Bound:13P Unbound Unbound
1adoB Unbound Bound:13P Unbound Unbound
1adoC Unbound Unbound Unbound Unbound
1adoD Unbound Unbound Unbound Unbound
1aldA Unbound Unbound Unbound Unbound
1epxA Unbound Unbound Unbound Unbound
1epxB Unbound Unbound Unbound Unbound
1epxC Unbound Unbound Unbound Unbound
1epxD Unbound Unbound Unbound Unbound
1ewdA Unbound Unbound Unbound Unbound
1ewdB Unbound Unbound Unbound Unbound
1ewdC Unbound Unbound Unbound Unbound
1ewdD Unbound Unbound Unbound Unbound
1eweA Unbound Unbound Unbound Unbound
1eweB Unbound Unbound Unbound Unbound
1eweC Unbound Unbound Unbound Unbound
1eweD Unbound Unbound Unbound Unbound
1ewgA Unbound Unbound Unbound Unbound
1ewgB Unbound Unbound Unbound Unbound
1ewgC Unbound Unbound Unbound Unbound
1ewgD Unbound Unbound Unbound Unbound
1ex5A Unbound Unbound Unbound Unbound
1ex5B Unbound Unbound Unbound Unbound
1ex5C Unbound Unbound Unbound Unbound
1ex5D Unbound Unbound Unbound Unbound
1f2jA Unbound Unbound Unbound Unbound
1fbaA Unbound Unbound Unbound Unbound
1fbaB Unbound Unbound Unbound Unbound
1fbaC Unbound Unbound Unbound Unbound
1fbaD Unbound Unbound Unbound Unbound
1j4eA Unbound Unbound Unbound Intermediate-bound:13P
1j4eB Unbound Unbound Unbound Intermediate-bound:13P
1j4eC Unbound Unbound Unbound Intermediate-bound:13P
1j4eD Unbound Unbound Unbound Intermediate-bound:13P
1qo5A Unbound Unbound Unbound Unbound
1qo5B Unbound Unbound Unbound Unbound
1qo5C Unbound Unbound Unbound Unbound
1qo5D Unbound Unbound Unbound Unbound
1qo5E Unbound Unbound Unbound Unbound
1qo5F Unbound Unbound Unbound Unbound
1qo5G Unbound Unbound Unbound Unbound
1qo5H Unbound Unbound Unbound Unbound
1qo5I Unbound Unbound Unbound Unbound
1qo5J Unbound Unbound Unbound Unbound
1qo5K Unbound Unbound Unbound Unbound
1qo5L Unbound Unbound Unbound Unbound
1qo5M Unbound Unbound Unbound Unbound
1qo5N Unbound Unbound Unbound Unbound
1qo5O Unbound Unbound Unbound Unbound
1qo5P Unbound Unbound Unbound Unbound
1qo5Q Unbound Unbound Unbound Unbound
1qo5R Unbound Unbound Unbound Unbound
2aldA Unbound Unbound Unbound Unbound
4aldA Bound:2FP Unbound Unbound Unbound
6aldA Bound:2FP Unbound Unbound Unbound
6aldB Bound:2FP Unbound Unbound Unbound
6aldC Unbound Unbound Unbound Unbound
6aldD Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [51] & [54]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1a5cA ASP 39;LYS 151;GLU 194;GLU 196;LYS 236
1a5cB ASP 39;LYS 151;GLU 194;GLU 196;LYS 236
1adoA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1adoB ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1adoC ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1adoD ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1aldA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1epxA ASP 43;LYS 156;GLU 197;GLU 199;LYS 239
1epxB ASP 43;LYS 156;GLU 197;GLU 199;LYS 239
1epxC ASP 43;LYS 156;GLU 197;GLU 199;LYS 239
1epxD ASP 43;LYS 156;GLU 197;GLU 199;LYS 239
1ewdA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1ewdB ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1ewdC ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1ewdD ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1eweA ASP 33;LYS 146;GLU 187;GLU 189; mutant K229M
1eweB ASP 33;LYS 146;GLU 187;GLU 189; mutant K229M
1eweC ASP 33;LYS 146;GLU 187;GLU 189; mutant K229M
1eweD ASP 33;LYS 146;GLU 187;GLU 189; mutant K229M
1ewgA ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187Q
1ewgB ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187Q
1ewgC ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187Q
1ewgD ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187Q
1ex5A ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187A
1ex5B ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187A
1ex5C ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187A
1ex5D ASP 33;LYS 146;;GLU 189;LYS 229 mutant E187A
1f2jA ASP 43;LYS 156;GLU 197;GLU 199;LYS 239
1fbaA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1fbaB ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1fbaC ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1fbaD ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1j4eA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1j4eB ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1j4eC ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1j4eD ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5A ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5B ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5C ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5D ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5E ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5F ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5G ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5H ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5I ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5J ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5K ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5L ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5M ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5N ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5O ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5P ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5Q ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
1qo5R ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
2aldA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
4aldA ASP 33;LYS 146;GLU 187;GLU 189;LYS 229
6aldA ASP 33; ;GLU 187;GLU 189;LYS 229 mutant K146A
6aldB ASP 33; ;GLU 187;GLU 189;LYS 229 mutant K146A
6aldC ASP 33; ;GLU 187;GLU 189;LYS 229 mutant K146A
6aldD ASP 33; ;GLU 187;GLU 189;LYS 229 mutant K146A

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[11]
SCHEME 3, p.135-136
[16]
SCHEME 1
[26]
Fig.1
[32]
Scheme 2
[33]
Fig.2, Fig.3, p.38-39 6
[34]
Scheme 1, p.12294, p.12996-12997 5
[40]
p.36-38
[41]
Scheme 1, p.2088-2089 6
[43]
p.12662-12663
[45]
p.295, Table 3
[46]
p.823
[47]
p.1149-1150
[51]
Fig.5, p.13874 10
[54]
p.9482

References
[1]
Resource
Comments
Medline ID
PubMed ID 4607364
Journal Biochemistry
Year 1974
Volume 13
Pages 4371-5
Authors Heron EJ, Caprioli RM
Title 18O studies of the mechanisms of yeast and muscle aldolases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 954748
Journal Eur J Biochem
Year 1976
Volume 66
Pages 95-104
Authors Lowe G, Pratt RF
Title Proton exchange of the pro-S hydrogen at C-1 in dihydroxyacetone phosphate, D-fructose 1,6-bisphosphate and D-fructose 1-phosphate catalysed by rabbit-muscle aldolase.
Related PDB
Related UniProtKB
[3]
Resource
Comments ACTIVE SITE.
Medline ID 76190154
PubMed ID 5453
Journal J Biol Chem
Year 1976
Volume 251
Pages 3057-62
Authors Hartman FC, Brown JP
Title Affinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase.
Related PDB
Related UniProtKB P00883
[4]
Resource
Comments
Medline ID
PubMed ID 911752
Journal Biochemistry
Year 1977
Volume 16
Pages 3988-94
Authors Pratt RF
Title Rabbit muscle aldolase catalyzed proton exchange of hydroxyacetone phosphate with solvent.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 18166
Journal Biochemistry
Year 1977
Volume 16
Pages 2966-71
Authors Strapazon E, Steck TL
Title Interaction of the aldolase and the membrane of human erythrocytes.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 540038
Journal Biochem J
Year 1979
Volume 183
Pages 663-7
Authors Stewart M, Morton DJ, Clarke FM
Title Changes associated with glycolytic-enzyme binding in the equatorial X-ray-diffraction pattern of glycerinated rabbit psoas muscle.
Related PDB
Related UniProtKB
[7]
Resource
Comments SUBSTRATE-BINDING SITE.
Medline ID 80046697
PubMed ID 499203
Journal Eur J Biochem
Year 1979
Volume 99
Pages 309-13
Authors Patthy L, Varadi A, Thesz J, Kovacs K
Title Identification of the C-1-phosphate-binding arginine residue of rabbit-muscle aldolase. Isolation of 1,2-cyclohexanedione-labeled peptide by chemisorption chromatography.
Related PDB
Related UniProtKB P00883
[8]
Resource
Comments
Medline ID
PubMed ID 293723
Journal Proc Natl Acad Sci U S A
Year 1979
Volume 76
Pages 6323-5
Authors Pontremoli S, Melloni E, Salamino F, Sparatore B, Michetti M, Horecker BL
Title Changes in activity of fructose-1,6-bisphosphate aldolase in livers of fasted rabbits and accumulation of crossreacting immune material.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7385224
Journal Tohoku J Exp Med
Year 1980
Volume 130
Pages 143-52
Authors Nakashima K, Ohtsuki M, Tuboi S
Title Membrane-bound fructose 1,6-bisphosphate aldolase: catalytic activity and mechanisms of desorption.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 6115420
Journal Philos Trans R Soc Lond B Biol Sci
Year 1981
Volume 293
Pages 209-14
Authors Millar JR, Shaw PJ, Stammers DK, Watson HC
Title The low-resolution structure of human muscle aldolase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 6115413
Journal Philos Trans R Soc Lond B Biol Sci
Year 1981
Volume 293
Pages 131-43
Authors Rose IA
Title Chemistry of proton abstraction by glycolytic enzymes (aldolase, isomerases and pyruvate kinase).
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7092833
Journal Biochem J
Year 1982
Volume 202
Pages 589-602
Authors Brindle KM, Brown FF, Campbell ID, Foxall DL, Simpson RJ
Title A 1H n.m.r. study of isotope exchange catalysed by glycolytic enzymes in the human erythrocyte.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 6838539
Journal Biochem Biophys Res Commun
Year 1983
Volume 110
Pages 578-83
Authors Grazi E, Trombetta G, Lanzara V
Title Fructose-1,6-bisphosphate-aldolase from rabbit muscle. Half of the sites reactivity at low temperature.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 6679317
Journal Biochem Int
Year 1983
Volume 6
Pages 53-61
Authors Kelkar SM, Kaklij GS
Title Mechanism of aldolase binding to erythrocyte membrane: Part II. Kinetic aspects.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 6406231
Journal Eur J Biochem
Year 1983
Volume 133
Pages 433-7
Authors Ovadi J, Mohamed Osman IR, Batke J
Title Interaction of the dissociable glycerol-3-phosphate dehydrogenase and fructose-1,6-bisphosphate aldolase. Quantitative analysis by an extrinsic fluorescence probe.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 6486803
Journal Arch Biochem Biophys
Year 1984
Volume 233
Pages 595-602
Authors Grazi E, Trombetta G
Title Fructose-1,6-bisphosphate aldolase from rabbit muscle: different catalytic behavior of the dihydroxyacetone phosphate binding sites at low temperature.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 6487321
Journal Biochem Biophys Res Commun
Year 1984
Volume 123
Pages 1069-75
Authors Sygusch J, Lehoux L, Beaudry D
Title Extreme X-ray sensitive modification of type I aldolases by blue dye ligand chromatography.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 4026283
Journal Appl Biochem Biotechnol
Year 1985
Volume 11
Pages 91-100
Authors Abraham M, Horvath L, Simon M, Szajani B, Boross L
Title Characterization and comparison of soluble and immobilized pig muscle aldolases.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 4066671
Journal J Biol Chem
Year 1985
Volume 260
Pages 15286-90
Authors Sygusch J, Boulet H, Beaudry D
Title Structure of rabbit muscle aldolase at low resolution.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 3942758
Journal Biochim Biophys Acta
Year 1986
Volume 869
Pages 185-91
Authors Swain MS, Lebherz HG
Title Specific, limited tryptic modification of wheat-germ fructose-bisphosphate aldolase subunits: destruction of catalytic activity but not of ability to establish precise subunit-subunit recognition.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 3569280
Journal Eur J Biochem
Year 1987
Volume 164
Pages 655-9
Authors Vertessy B, Ovadi J
Title A simple approach to detect active-site-directed enzyme-enzyme interactions. The aldolase/glycerol-phosphate-dehydrogenase enzyme system.
Related PDB
Related UniProtKB
[22]
Resource
Comments VARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID 88068641
PubMed ID 2825199
Journal Proc Natl Acad Sci U S A
Year 1987
Volume 84
Pages 8623-7
Authors Kishi H, Mukai T, Hirono A, Fujii H, Miwa S, Hori K
Title Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation.
Related PDB
Related UniProtKB P04075
[23]
Resource
Comments
Medline ID
PubMed ID 2556962
Journal Appl Biochem Biotechnol
Year 1989
Volume 22
Pages 223-35
Authors Horvath L, Abraham M, Boross L, Szajani B
Title Immobilization of pig muscle aldolase on a silica-based support.
Related PDB
Related UniProtKB
[24]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID 90242948
PubMed ID 2335208
Journal FEBS Lett
Year 1990
Volume 262
Pages 282-6
Authors Gamblin SJ, Cooper B, Millar JR, Davies GJ, Littlechild JA, Watson HC
Title The crystal structure of human muscle aldolase at 3.0 A resolution.
Related PDB
Related UniProtKB P04075
[25]
Resource
Comments VARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID 91035340
PubMed ID 2229018
Journal J Biochem (Tokyo)
Year 1990
Volume 108
Pages 153-7
Authors Takasaki Y, Takahashi I, Mukai T, Hori K
Title Human aldolase A of a hemolytic anemia patient with Asp-128----Gly substitution: characteristics of an enzyme generated in E. coli transfected with the expression plasmid pHAAD128G.
Related PDB
Related UniProtKB P04075
[26]
Resource
Comments
Medline ID
PubMed ID 1814134
Journal Acta Biochim Pol
Year 1991
Volume 38
Pages 407-21
Authors Kochman M, Dobryszycki P
Title Topography and conformational changes of fructose-1,6-bisphosphate aldolase.
Related PDB
Related UniProtKB
[27]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 92070498
PubMed ID 1959612
Journal FEBS Lett
Year 1991
Volume 292
Pages 237-42
Authors Hester G, Brenner-Holzach O, Rossi FA, Struck-Donatz M, Winterhalter KH, Smit JD, Piontek K
Title The crystal structure of fructose-1,6-bisphosphate aldolase from Drosophila melanogaster at 2.5 A resolution.
Related PDB 1fba
Related UniProtKB P07764
[28]
Resource
Comments
Medline ID
PubMed ID 1894606
Journal J Biol Chem
Year 1991
Volume 266
Pages 17099-105
Authors Berthiaume L, Loisel TP, Sygusch J
Title Carboxyl terminus region modulates catalytic activity of recombinant maize aldolase.
Related PDB
Related UniProtKB
[29]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 91278081
PubMed ID 2056525
Journal J Mol Biol
Year 1991
Volume 219
Pages 573-6
Authors Gamblin SJ, Davies GJ, Grimes JM, Jackson RM, Littlechild JA, Watson HC
Title Activity and specificity of human aldolases.
Related PDB 1ald
Related UniProtKB P04075
[30]
Resource
Comments
Medline ID
PubMed ID 1417758
Journal Biochem J
Year 1992
Volume 286
Pages 977-9
Authors Vertessy BG, Vas M
Title Metabolite channeling versus free diffusion: reinterpretation of aldolase-catalysed inactivation of glyceraldehyde-3-phosphate dehydrogenase.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 1577806
Journal J Biol Chem
Year 1992
Volume 267
Pages 9713-7
Authors Rae C, Bubb WA, Kuchel PW
Title Aldolase-catalyzed diketone phosphate formation from oxoaldehydes. NMR studies and metabolic significance.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 8513801
Journal Eur J Biochem
Year 1993
Volume 214
Pages 515-9
Authors Gupta S, Hollenstein R, Kochhar S, Christen P
Title Paracatalytic self-inactivation of fructose-1,6-bisphosphate aldolase. Structure of the crosslink formed at the active site.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 8488556
Journal Trends Biochem Sci
Year 1993
Volume 18
Pages 36-9
Authors Littlechild JA, Watson HC
Title A data-based reaction mechanism for type I fructose bisphosphate aldolase.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 7918450
Journal Biochemistry
Year 1994
Volume 33
Pages 12291-7
Authors Morris AJ, Tolan DR
Title Lysine-146 of rabbit muscle aldolase is essential for cleavage and condensation of the C3-C4 bond of fructose 1,6-bis(phosphate).
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 8527430
Journal Biochemistry
Year 1995
Volume 34
Pages 16574-84
Authors Schneider ML, Post CB
Title Solution structure of a band 3 peptide inhibitor bound to aldolase: a proposed mechanism for regulating binding by tyrosine phosphorylation.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 8636111
Journal J Biol Chem
Year 1996
Volume 271
Pages 6861-5
Authors Wang J, Morris AJ, Tolan DR, Pagliaro L
Title The molecular nature of the F-actin binding activity of aldolase revealed with site-directed mutants.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 8643582
Journal Proc Natl Acad Sci U S A
Year 1996
Volume 93
Pages 5374-9
Authors Beernink PT, Tolan DR
Title Disruption of the aldolase A tetramer into catalytically active monomers.
Related PDB
Related UniProtKB
[38]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal Protein Pept Lett
Year 1996
Volume 3
Pages 207-12
Authors Dalby A, Rawas A, Watson HC, Littlechild JA
Title Crystallisation and Preliminary X-Ray Diffraction Studies on Human Liver Aldolase.
Related PDB 1qo5
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 9325270
Journal J Biol Chem
Year 1997
Volume 272
Pages 25542-6
Authors Vertessy BG, Orosz F, Kovacs J, Ovadi J
Title Alternative binding of two sequential glycolytic enzymes to microtubules. Molecular studies in the phosphofructokinase/aldolase/microtubule system.
Related PDB
Related UniProtKB
[40]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 97143309
PubMed ID 8989320
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 36-9
Authors Blom N, Sygusch J
Title Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase.
Related PDB 1ado
Related UniProtKB P00883
[41]
Resource
Comments
Medline ID
PubMed ID 9405338
Journal Science
Year 1997
Volume 278
Pages 2085-92
Authors Barbas CF 3rd, Heine A, Zhong G, Hoffmann T, Gramatikova S, Bjornestedt R, List B, Anderson J, Stura EA, Wilson IA, Lerner RA
Title Immune versus natural selection: antibody aldolases with enzymic rates but broader scope.
Related PDB
Related UniProtKB
[42]
Resource
Comments X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID 98190013
PubMed ID 9521758
Journal Biochemistry
Year 1998
Volume 37
Pages 4388-96
Authors Kim H, Certa U, Dobeli H, Jakob P, Hol WG
Title Crystal structure of fructose-1,6-bisphosphate aldolase from the human malaria parasite Plasmodium falciparum.
Related PDB 1a5c
Related UniProtKB P14223
[43]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10504235
Journal Biochemistry
Year 1999
Volume 38
Pages 12655-64
Authors Choi KH, Mazurkie AS, Morris AJ, Utheza D, Tolan DR, Allen KN
Title Structure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 A(,).
Related PDB 6ald
Related UniProtKB
[44]
Resource
Comments
Medline ID
PubMed ID 10336621
Journal Eur J Biochem
Year 1999
Volume 262
Pages 371-6
Authors Pettersson H, Pettersson G
Title Mechanism of metabolite transfer in coupled two-enzyme reactions involving aldolase.
Related PDB
Related UniProtKB
[45]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID 99156067
PubMed ID 10048322
Journal Protein Sci
Year 1999
Volume 8
Pages 291-7
Authors Dalby A, Dauter Z, Littlechild JA
Title Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications.
Related PDB 2ald 4ald
Related UniProtKB P04075
[46]
Resource
Comments
Medline ID
PubMed ID 10970798
Journal Biochem J
Year 2000
Volume 350 Pt 3
Pages 823-8
Authors Santamaria R, Esposito G, Vitagliano L, Race V, Paglionico I, Zancan L, Zagari A, Salvatore F
Title Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase.
Related PDB
Related UniProtKB
[47]
Resource
Comments
Medline ID
PubMed ID 10625657
Journal J Biol Chem
Year 2000
Volume 275
Pages 1145-51
Authors Rellos P, Sygusch J, Cox TM
Title Expression, purification, and characterization of natural mutants of human aldolase B. Role of quaternary structure in catalysis.
Related PDB
Related UniProtKB
[48]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10891264
Journal J Mol Biol
Year 2000
Volume 300
Pages 697-707
Authors Chudzik DM, Michels PA, de Walque S, Hol WG
Title Structures of type 2 peroxisomal targeting signals in two trypanosomatid aldolases.
Related PDB 1epx 1f2j
Related UniProtKB P07752
[49]
Resource
Comments
Medline ID
PubMed ID 10959854
Journal J Org Chem
Year 2000
Volume 65
Pages 4529-31
Authors Chenevert R, Dasser M
Title Chemoenzymatic synthesis of the microbial elicitor (-)-syringolide via a fructose 1,6-diphosphate aldolase-catalyzed condensation reaction.
Related PDB
Related UniProtKB
[50]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
Medline ID
PubMed ID 11679716
Journal Acta Crystallogr D Biol Crystallogr
Year 2001
Volume 57
Pages 1526-33
Authors Dalby AR, Tolan DR, Littlechild JA
Title The structure of human liver fructose-1,6-bisphosphate aldolase.
Related PDB
Related UniProtKB P05062
[51]
Resource
Comments
Medline ID
PubMed ID 11705376
Journal Biochemistry
Year 2001
Volume 40
Pages 13868-75
Authors Choi KH, Shi J, Hopkins CE, Tolan DR, Allen KN
Title Snapshots of catalysis: the structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate.
Related PDB 1j4e
Related UniProtKB
[52]
Resource
Comments
Medline ID
PubMed ID 11371431
Journal Biophys J
Year 2001
Volume 80
Pages 2527-35
Authors Ouporov IV, Knull HR, Huber A, Thomasson KA
Title Brownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling.
Related PDB
Related UniProtKB
[53]
Resource
Comments
Medline ID
PubMed ID 12417303
Journal FEBS Lett
Year 2002
Volume 531
Pages 152-6
Authors Esposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F
Title Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance.
Related PDB
Related UniProtKB
[54]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11779856
Journal J Biol Chem
Year 2002
Volume 277
Pages 9474-83
Authors Maurady A, Zdanov A, de Moissac D, Beaudry D, Sygusch J
Title A conserved glutamate residue exhibits multifunctional catalytic roles in D-fructose-1,6-bisphosphate aldolases.
Related PDB 1ewd 1ewe 1ewg 1ex5
Related UniProtKB
[55]
Resource
Comments
Medline ID
PubMed ID 11835505
Journal Proteins
Year 2002
Volume 46
Pages 295-307
Authors Zabell AP, Post CB
Title Docking multiple conformations of a flexible ligand into a protein binding site using NMR restraints.
Related PDB
Related UniProtKB
[56]
Resource
Comments
Medline ID
PubMed ID 15025449
Journal J Am Chem Soc
Year 2004
Volume 126
Pages 3402-3
Authors Choi KH, Tolan DR
Title Presteady-state kinetic evidence for a ring-opening activity in fructose-1,6-(bis)phosphate aldolase.
Related PDB
Related UniProtKB

Comments
This enzyme is class I aldolase. The class II aldolase (S00235 in EzCatDB) has got totally different mechanism with zinc ion at the active site.
The literature [51] & [54] indicate different catalytic residues. Accoridng to the literature [51], Glu187 plays a catalytic role by protonating the C2-hydroxyl group during Schiff-base formation, and Asp33 is involved in C3-C4 bond cleavage. In contrast, Glu187 is involved in the bond cleavage, according to the literature [54]. (The active site structures support the literature [54].)
According to the literature [51], [54] & [56], the catalytic reaction of this enzyme may proceeds as follows;
(A) Eliminative double-bond formation; Ring-opening/hemiketal cleavage
(B) Exchange of double-bonded atoms; Schiff-base formation
(B1) Glu187 acts as a general base to abstract a proton from the sidechain of Lys229, enhancing its nucleophilicity (see [54]). Here, the function of Glu187 is modulated by Glu189.
(B2) The activated Lys229 makes a nucleophilic attack on C2-carbonyl group, to form a carbinolamine intermediate. (Here, a proton must transfer from the sidechain amine of Lys229 to the C2-carbonyl oxygen, with a probable assistance by Glu187. Glu187 may protonate the C2-carbonyl oxygen, and then deprotonate the amine of Lys229.)
(B3) The lone pair of Lys229 makes another attak on C2-carbon, whilst Glu187 acts as a general acid to protonate the eliminated hydroxyl group. This reaction leads to Schiff-base intermeidate formation.
(C) Eliminative double-bond formation;C3-C4 bond cleavage
(C1) Glu187 acts as a general base to deprotonate C4-hydroxyl group, leading to the C3-C4 bond cleavage (see [54]). Here, the electron sink (Schiff-base) formed at C2 facilitate the deprotonation, and formation of C2=C3 double-bond, or ketamine (or enamine) intermediate. (According to the literature [1], instead of Glu187, Asp33 acts as the base.)
(C2) The first product, G3P, is released from the active site.
(D) Isomerization; Shift of double-bond
(D1) The lone pair at nitrogen atom of Lys229 makes an attack on C2 carbon, to form Schiff-base again, which leads to C3-carbanion intermediate. The carbanion seems to be stabilized by the protonated sidechain of Lys146.
(D2) Asp33 protonates the carbanion, to form an imine intermediate.
(E) Exchange of double-bonded atoms; Schiff-base deformation
(E1) Glu187 acts as a general base, to activate a water molecule.
(E2) The activated water makes a nucleophilic attack on the C2 carbon, to form a carbinolamine intermeidate. (Here, a proton must transfer from the hydroxyl group to the sidechain amine of Lys229, with a probable assistance by Glu187. Glu187 may protonate the sidechain of Lys229, and then deprotonate the hydroxyl group.)
(E3) The lone pair at the hydroxyl group of carbinolamine makes a nucleophilic attack on the C2 carbon again, to release the sidechain of Lys229.
(E4) Unprotonated Lys229 must be protonated by Glu187.

Created Updated
2004-05-24 2009-02-26