S00235
type: Enzyme
rlcp: p451
cath: TIM Barrel
ec: https://purl.uniprot.org/enzyme/4.1.2.13
csa: 1b57
macie: M0052
uniprot: P0AB71
kegg enzyme: fructose-bisphosphate aldolase
kegg enzyme: aldolase
kegg enzyme: fructose-1,6-bisphosphate triosephosphate-lyase
kegg enzyme: fructose diphosphate aldolase
kegg enzyme: diphosphofructose aldolase
kegg enzyme: fructose 1,6-diphosphate aldolase
kegg enzyme: ketose 1-phosphate aldolase
kegg enzyme: phosphofructoaldolase
kegg enzyme: zymohexase
kegg enzyme: fructoaldolase
kegg enzyme: fructose 1-phosphate aldolase
kegg enzyme: fructose 1-monophosphate aldolase
kegg enzyme: 1,6-Diphosphofructose aldolase
kegg enzyme: SMALDO
kegg enzyme: D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase
kegg pathway: Glycolysis / Gluconeogenesis
kegg pathway: Pentose phosphate pathway
kegg pathway: Fructose and mannose metabolism
kegg pathway: Carbon fixation in photosynthetic organisms
kegg cofactor: Zinc
kegg cofactor: Monovalent metal
kegg substrate: D-Fructose 1,6-bisphosphate
kegg product: Glycerone phosphate
kegg product: D-Glyceraldehyde 3-phosphate
pdb: 1b57A
pdb: 1b57B
pdb: 1dosA
pdb: 1dosB
pdb: 1zenA
pdb: 1gynA
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1b57A
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1b57B
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1dosA
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1dosB
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1zenA
pdb bound state: Unbound
  compound: D-Fructose 1,6-bisphosphate
  pdb: 1gynA
pdb bound state: Analogue
  compound: Zinc
  pdb: 1gynA
  ligand het code: _CD_401
pdb bound state: Unbound
  compound: Monovalent metal
  pdb: 1dosA
pdb bound state: Unbound
  compound: Monovalent metal
  pdb: 1dosB
pdb bound state: Unbound
  compound: Monovalent metal
  pdb: 1zenA
pdb bound state: Unbound
  compound: Monovalent metal
  pdb: 1gynA
pdb bound state: Analogue
  compound: Glycerone phosphate
  pdb: 1b57A
  ligand het code: PGH
pdb bound state: Analogue
  compound: Glycerone phosphate
  pdb: 1b57B
  ligand het code: PGH
pdb bound state: Unbound
  compound: Glycerone phosphate
  pdb: 1dosA
pdb bound state: Unbound
  compound: Glycerone phosphate
  pdb: 1dosB
pdb bound state: Unbound
  compound: Glycerone phosphate
  pdb: 1zenA
pdb bound state: Unbound
  compound: Glycerone phosphate
  pdb: 1gynA
pdb bound state: Unbound
  compound: D-Glyceraldehyde 3-phosphate
  pdb: 1b57A
pdb bound state: Unbound
  compound: D-Glyceraldehyde 3-phosphate
  pdb: 1b57B
active site residues resources: Identification of arginine 331 as an important active site residue in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli.
active site residues resources: Epimerization via carbon-carbon bond cleavage. L-ribulose-5-phosphate 4-epimerase as a masked class II aldolase.
active site residues resources: Conserved residues in the mechanism of the E. coli Class II FBP-aldolase.
active site residues resources: P0AB71
references: Magnetic resonance studies of the role of the divalent cation in the mechanism of yeast aldolase.
references: 18O studies of the mechanisms of yeast and muscle aldolases.
references: Initiating a crystallographic study of a class II fructose-1,6-bisphosphate aldolase.
references: Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli.
references: Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis.
references: Functional characterization of an extreme thermophilic class II fructose-1,6-bisphosphate aldolase.
references: http://ezcatdb.cbrc.jp/EzCatDB/reference/S00235#7
references: Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase.
references: Identification of arginine 331 as an important active site residue in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli.
references: The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold.
references: Epimerization via carbon-carbon bond cleavage. L-ribulose-5-phosphate 4-epimerase as a masked class II aldolase.
references: The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity.
references: Conserved residues in the mechanism of the E. coli Class II FBP-aldolase.
references: Exploring substrate binding and discrimination in fructose1, 6-bisphosphate and tagatose 1,6-bisphosphate aldolases.
references: Crystallization and preliminary X-ray analysis of native and selenomethionine fructose-1,6-bisphosphate aldolase from Thermus aquaticus.
references: Brownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling.
references: Molecular cloning, expression, purification, and characterization of fructose-1,6-bisphosphate aldolase from Thermus aquaticus.
references: A functional role for a flexible loop containing Glu182 in the class II fructose-1,6-bisphosphate aldolase from Escherichia coli.
references: The organization of divalent cations in the active site of cadmium Escherichia coli fructose-1,6-bisphosphate aldolase.
comment: Although Glu174 is bound to the catalytic zinc ion, it moves away from the zinc ion to allow the substrate/product (Glycerone phosphate; GP) moiety to coordinate the ion during the catalysis (see [10]). Here, zinc ion functions as a Lewis acid electron sink, and polarizes the carbonyl bond of GP, for the elimination or addition reaction. A monovalent cation is required for substrate binding, although it is not involved in catalysis. According to the literature [18], although Glu182 is distant from the active site in the absence of substrate, it would be brought into a position to act as a general base on binding of substrates. This enzyme catalyzes two reverse reactions, which are composed of two reactions respectively (see [12]): (#1) the aldol condensation of a ketose, Glycerone phosphate (GP) and an aldose, glyceraldehyde 3-phosphate (G3P) to form the acyclic form of fructose 1,6-bisphospahte (FBP); that is addition of GP to the double-bond (carbonyl group) of G3P. (In Gluconeogenesis pathway) (A) Isomerization: (B) Addition of GP to the double-bond (carbonyl group) of G3P: (#2) the clevage of FBP into GP and G3P; that is elimination of GP from FBP to form a new double-bond in another product, G3P. (In glycolysis pathway) (C) Elimination of GP: (D) Isomerization: These catalytic reactions proceeds as follows (see [12] & [18]): (A) Isomerization: (A1) Carbonyl group and hydroxyl group of GP are bound to the catalytic zinc ion, replacing Glu174. Here, the zinc ion polarizes the carbonyl bond of the ketose substrate, GP, which increases the acidity of the hydroxymethylene (C1) hydrogen atoms, facilitating the next reaction, deprotonation. (A2) Glu182 acts as a general base to deprotonate the C1 atom, leading to the formation of ene-diolate (carbanion) intermediate. This intermediate is stabilized by Asn286. (B) Addition of the ene-diolate intermediate to the double-bond (carbonyl group) of G3P (B1) The second substrate (aldehyde), G3P, which is electrophilic, binds …

TIM Barrel
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.20.20.70
catalytic domain: index.html

Glycolysis / Gluconeogenesis
type: KeggPathway
references: KEGG:MAP00010

Pentose phosphate pathway
type: KeggPathway
references: KEGG:MAP00030

Fructose and mannose metabolism
type: KeggPathway
references: KEGG:MAP00051

Carbon fixation in photosynthetic organisms
type: KeggPathway
references: KEGG:MAP00710

Zinc
type: KeggCofactor
references: KEGG:C00038
compound type: heavy metal
references: CHEBI:29105
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Monovalent metal
type: KeggCofactor
references: KEGG:C99999
compound type: univalent metal (Na+, K+)

D-Fructose 1,6-bisphosphate
type: KeggSubstrate
references: KEGG:C00354
compound type: carbohydrate
compound type: phosphate group/phosphate ion
references: CHEBI:37736
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Glycerone phosphate
type: KeggProduct
references: KEGG:C00111
compound type: carbohydrate
compound type: phosphate group/phosphate ion
references: CHEBI:16108
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

D-Glyceraldehyde 3-phosphate
type: KeggProduct
references: KEGG:C00118
compound type: carbohydrate
compound type: phosphate group/phosphate ion
references: CHEBI:29052
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1b57A
type: Pdb
references: 1b57
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1b57
catalytic residue: ASP 109;GLU 182;ASN 286
cofactor binding residue: HIS 110;GLU 174;HIS 226;HIS 264(Catalytic zinc);VAL 225;GLY 227;GLY 265;SER 267(Monovalent metal)

1b57B
type: Pdb
references: 1b57
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1b57
catalytic residue: ASP 109;GLU 182;ASN 286
cofactor binding residue: HIS 110;GLU 174;HIS 226;HIS 264(Catalytic zinc);VAL 225;GLY 227;GLY 265;SER 267(Monovalent metal)

1dosA
type: Pdb
references: 1dos
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dos
catalytic residue: ASP 109;GLU 182;ASN 286
cofactor binding residue: HIS 110;GLU 174;HIS 226;HIS 264(Catalytic zinc);VAL 225;GLY 227;GLY 265;SER 267(Monovalent metal)

1dosB
type: Pdb
references: 1dos
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dos
catalytic residue: ASP 109;GLU 182;ASN 286
cofactor binding residue: HIS 110;GLU 174;HIS 226;HIS 264(Catalytic zinc);VAL 225;GLY 227;GLY 265;SER 267(Monovalent metal)

1zenA
type: Pdb
references: 1zen
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1zen
catalytic residue: ASP 109; ;ASN 286
cofactor binding residue: HIS 110;GLU 174;HIS 226;HIS 264(Catalytic zinc);VAL 225;GLY 227;GLY 265;SER 267(Monovalent metal)
comment: invisible 177-193

1gynA
type: Pdb
references: 1gyn
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1gyn
catalytic residue: ASP 109; ;ASN 286
cofactor binding residue: HIS 110;GLU 174; ;HIS 264(Catalytic zinc);VAL 225; ;GLY 265;SER 267(Monovalent metal)
comment: invisible 177-193, 226-243

Magnetic resonance studies of the role of the divalent cation in the mechanism of yeast aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4324205
journal: Biochemistry
volume: 10
pages: 1191-204
published year: 1971
authors:
  item: Mildvan AS
  item: Kobes RD
  item: Rutter WJ

18O studies of the mechanisms of yeast and muscle aldolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/4607364
journal: Biochemistry
volume: 13
pages: 4371-5
published year: 1974
authors:
  item: Heron EJ
  item: Caprioli RM

Initiating a crystallographic study of a class II fructose-1,6-bisphosphate aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/1613797
journal: J Mol Biol
volume: 225
pages: 1137-41
published year: 1992
authors:
  item: Naismith JH
  item: Ferrara JD
  item: Bailey S
  item: Marshall K
  item: Dauter Z
  item: Wilson KS
  item: Habash J
  item: Harrop SJ
  item: Berry AJ
  item: Hunter WN

Identification of zinc-binding ligands in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli.
type: BibliographicResource
comment: ZINC-LIGANDS, AND MUTAGENESIS.
medline id: 93170474
references: http://www.ncbi.nlm.nih.gov/pubmed/8436219
journal: FEBS Lett
volume: 318
pages: 11-6
published year: 1993
authors:
  item: Berry A
  item: Marshall KE
references: P0AB71

Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/7872790
journal: Arch Biochem Biophys
volume: 317
pages: 244-52
published year: 1995
authors:
  item: Szwergold BS
  item: Ugurbil K
  item: Brown TR

Functional characterization of an extreme thermophilic class II fructose-1,6-bisphosphate aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8898912
journal: Eur J Biochem
volume: 241
pages: 243-8
published year: 1996
authors:
  item: De Montigny C
  item: Sygusch J

http://ezcatdb.cbrc.jp/EzCatDB/reference/S00235#7
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9174952
journal: J Mol Recognit
volume: 9
pages: 652-7
published year: 1996
authors:
  item: Nicholls IA
  item: Matsui J
  item: Krook M
  item: Mosbach K
title: Some recent developments in the preparation of novel recognition systems: a recognition site for the selective catalysis of an aldol condensation using molecular imprinting and specific affinity motifs for alpha-chymotrypsin using a phage display peptide library.

Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS).
medline id: 96433074
references: http://www.ncbi.nlm.nih.gov/pubmed/8836102
journal: Nat Struct Biol
volume: 3
pages: 856-62
published year: 1996
authors:
  item: Blom NS
  item: Tetreault S
  item: Coulombe R
  item: Sygusch J
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P0AB71

Identification of arginine 331 as an important active site residue in the class II fructose-1,6-bisphosphate aldolase of Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/8771208
journal: Protein Sci
volume: 5
pages: 154-61
published year: 1996
authors:
  item: Qamar S
  item: Marsh K
  item: Berry A

The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
medline id: 97094986
references: http://www.ncbi.nlm.nih.gov/pubmed/8939754
journal: Structure
volume: 4
pages: 1303-15
published year: 1996
authors:
  item: Cooper SJ
  item: Leonard GA
  item: McSweeney SM
  item: Thompson AW
  item: Naismith JH
  item: Qamar S
  item: Plater A
  item: Berry A
  item: Hunter WN
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P0AB71

Epimerization via carbon-carbon bond cleavage. L-ribulose-5-phosphate 4-epimerase as a masked class II aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9548961
journal: Biochemistry
volume: 37
pages: 5746-54
published year: 1998
authors:
  item: Johnson AE
  item: Tanner ME

The crystal structure of Escherichia coli class II fructose-1, 6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
medline id: 99182425
references: http://www.ncbi.nlm.nih.gov/pubmed/10080900
journal: J Mol Biol
volume: 287
pages: 383-94
published year: 1999
authors:
  item: Hall DR
  item: Leonard GA
  item: Reed CD
  item: Watt CI
  item: Berry A
  item: Hunter WN
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P0AB71

Conserved residues in the mechanism of the E. coli Class II FBP-aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9878448
journal: J Mol Biol
volume: 285
pages: 843-55
published year: 1999
authors:
  item: Plater AR
  item: Zgiby SM
  item: Thomson GJ
  item: Qamar S
  item: Wharton CW
  item: Berry A

Exploring substrate binding and discrimination in fructose1, 6-bisphosphate and tagatose 1,6-bisphosphate aldolases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10712619
journal: Eur J Biochem
volume: 267
pages: 1858-68
published year: 2000
authors:
  item: Zgiby SM
  item: Thomson GJ
  item: Qamar S
  item: Berry A

Crystallization and preliminary X-ray analysis of native and selenomethionine fructose-1,6-bisphosphate aldolase from Thermus aquaticus.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11173490
journal: Acta Crystallogr D Biol Crystallogr
volume: 57
pages: 310-3
published year: 2001
authors:
  item: Sauve V
  item: Sygusch J

Brownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11371431
journal: Biophys J
volume: 80
pages: 2527-35
published year: 2001
authors:
  item: Ouporov IV
  item: Knull HR
  item: Huber A
  item: Thomasson KA

Molecular cloning, expression, purification, and characterization of fructose-1,6-bisphosphate aldolase from Thermus aquaticus.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11237691
journal: Protein Expr Purif
volume: 21
pages: 293-302
published year: 2001
authors:
  item: Sauve V
  item: Sygusch J

A functional role for a flexible loop containing Glu182 in the class II fructose-1,6-bisphosphate aldolase from Escherichia coli.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11779234
journal: J Mol Biol
volume: 315
pages: 131-40
published year: 2002
authors:
  item: Zgiby S
  item: Plater AR
  item: Bates MA
  item: Thomson GJ
  item: Berry A

The organization of divalent cations in the active site of cadmium Escherichia coli fructose-1,6-bisphosphate aldolase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12595741
journal: Acta Crystallogr D Biol Crystallogr
volume: 59
pages: 611-4
published year: 2003
authors:
  item: Hall DR
  item: Kemp LE
  item: Leonard GA
  item: Marshall K
  item: Berry A
  item: Hunter WN

ReferenceForCatalyticMechanism
reference index: 1
reference section: Fig.9, p.1203-1204
reference step: 2

ReferenceForCatalyticMechanism
reference index: 5
reference section: p.250-251

ReferenceForCatalyticMechanism
reference index: 8
reference section: p.858-859

ReferenceForCatalyticMechanism
reference index: 9
reference section: Fig.5, p.157

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.1307-1310

ReferenceForCatalyticMechanism
reference index: 12
reference section: Fig.6, p.389-391
reference step: 5

ReferenceForCatalyticMechanism
reference index: 13
reference section: Fig.3, p.852

ReferenceForCatalyticMechanism
reference index: 14
reference section: Fig.1
reference step: 5

ReferenceForCatalyticMechanism
reference index: 18
reference section: Fig.2, p.137-138
reference step: 6