EzCatDB: S00199
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00199
RLCP classification6.10.400600.113 : Double-bonded atom exchange
5.121.671000.6111 : Elimination
8.112.3600000.6580 : Isomerization
6.20.7800.6111 : Double-bonded atom exchange
CATH domainDomain 13.20.20.70 : TIM BarrelCatalytic domain
E.C.4.1.2.13
CSA1ald

CATH domainRelated DB codes (homologues)
3.20.20.70 : TIM BarrelS00215,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

Enzyme Name
UniProtKBKEGG

P04075P05062P00883P07764P14223P07752
Protein nameFructose-bisphosphate aldolase AFructose-bisphosphate aldolase BFructose-bisphosphate aldolase AFructose-bisphosphate aldolaseFructose-bisphosphate aldolaseFructose-bisphosphate aldolase, glycosomalfructose-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
SynonymsEC 4.1.2.13
Muscle-type aldolase
Lung cancer antigen NY-LU-1
EC 4.1.2.13
Liver-type aldolase
EC 4.1.2.13
Muscle-type aldolase
EC 4.1.2.13
EC 4.1.2.13
41 kDa antigen
EC 4.1.2.13
RefSeqNP_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)
NP_000026.2 (Protein)
NM_000035.3 (DNA/RNA sequence)
NP_001075707.1 (Protein)
NM_001082238.1 (DNA/RNA sequence)
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)


PfamPF00274 (Glycolytic)
[Graphical view]
PF00274 (Glycolytic)
[Graphical view]
PF00274 (Glycolytic)
[Graphical view]
PF00274 (Glycolytic)
[Graphical view]
PF00274 (Glycolytic)
[Graphical view]
PF00274 (Glycolytic)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00010Glycolysis / Gluconeogenesis
MAP00030Pentose phosphate pathway
MAP00051Fructose and mannose metabolism
MAP00710Carbon fixation in photosynthetic organisms

UniProtKB:Accession NumberP04075P05062P00883P07764P14223P07752
Entry nameALDOA_HUMANALDOB_HUMANALDOA_RABITALF_DROMEALF_PLAFAALF_TRYBB
ActivityD-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.
SubunitHomotetramer.Homotetramer.Tetramer.Homotetramer.Homotetramer.
Subcellular location




Glycosome.
Cofactor






Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00354C00111C00118
CompoundD-Fructose 1,6-bisphosphateGlycerone phosphateD-Glyceraldehyde 3-phosphateIntermediate
Typecarbohydrate,phosphate group/phosphate ioncarbohydrate,phosphate group/phosphate ioncarbohydrate,phosphate group/phosphate ion
ChEBI37736
16108
29052

PubChem172313
668
439168

            
1a5cAUnboundUnboundUnboundUnbound
1a5cBUnboundUnboundUnboundUnbound
1adoAUnboundBound:13PUnboundUnbound
1adoBUnboundBound:13PUnboundUnbound
1adoCUnboundUnboundUnboundUnbound
1adoDUnboundUnboundUnboundUnbound
1aldAUnboundUnboundUnboundUnbound
1epxAUnboundUnboundUnboundUnbound
1epxBUnboundUnboundUnboundUnbound
1epxCUnboundUnboundUnboundUnbound
1epxDUnboundUnboundUnboundUnbound
1ewdAUnboundUnboundUnboundUnbound
1ewdBUnboundUnboundUnboundUnbound
1ewdCUnboundUnboundUnboundUnbound
1ewdDUnboundUnboundUnboundUnbound
1eweAUnboundUnboundUnboundUnbound
1eweBUnboundUnboundUnboundUnbound
1eweCUnboundUnboundUnboundUnbound
1eweDUnboundUnboundUnboundUnbound
1ewgAUnboundUnboundUnboundUnbound
1ewgBUnboundUnboundUnboundUnbound
1ewgCUnboundUnboundUnboundUnbound
1ewgDUnboundUnboundUnboundUnbound
1ex5AUnboundUnboundUnboundUnbound
1ex5BUnboundUnboundUnboundUnbound
1ex5CUnboundUnboundUnboundUnbound
1ex5DUnboundUnboundUnboundUnbound
1f2jAUnboundUnboundUnboundUnbound
1fbaAUnboundUnboundUnboundUnbound
1fbaBUnboundUnboundUnboundUnbound
1fbaCUnboundUnboundUnboundUnbound
1fbaDUnboundUnboundUnboundUnbound
1j4eAUnboundUnboundUnboundIntermediate-bound:13P
1j4eBUnboundUnboundUnboundIntermediate-bound:13P
1j4eCUnboundUnboundUnboundIntermediate-bound:13P
1j4eDUnboundUnboundUnboundIntermediate-bound:13P
1qo5AUnboundUnboundUnboundUnbound
1qo5BUnboundUnboundUnboundUnbound
1qo5CUnboundUnboundUnboundUnbound
1qo5DUnboundUnboundUnboundUnbound
1qo5EUnboundUnboundUnboundUnbound
1qo5FUnboundUnboundUnboundUnbound
1qo5GUnboundUnboundUnboundUnbound
1qo5HUnboundUnboundUnboundUnbound
1qo5IUnboundUnboundUnboundUnbound
1qo5JUnboundUnboundUnboundUnbound
1qo5KUnboundUnboundUnboundUnbound
1qo5LUnboundUnboundUnboundUnbound
1qo5MUnboundUnboundUnboundUnbound
1qo5NUnboundUnboundUnboundUnbound
1qo5OUnboundUnboundUnboundUnbound
1qo5PUnboundUnboundUnboundUnbound
1qo5QUnboundUnboundUnboundUnbound
1qo5RUnboundUnboundUnboundUnbound
2aldAUnboundUnboundUnboundUnbound
4aldABound:2FPUnboundUnboundUnbound
6aldABound:2FPUnboundUnboundUnbound
6aldBBound:2FPUnboundUnboundUnbound
6aldCUnboundUnboundUnboundUnbound
6aldDUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [51] & [54]
pdbCatalytic residuescomment
          
1a5cAASP 39;LYS 151;GLU 194;GLU 196;LYS 236
 
1a5cBASP 39;LYS 151;GLU 194;GLU 196;LYS 236
 
1adoAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1adoBASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1adoCASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1adoDASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1aldAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1epxAASP 43;LYS 156;GLU 197;GLU 199;LYS 239
 
1epxBASP 43;LYS 156;GLU 197;GLU 199;LYS 239
 
1epxCASP 43;LYS 156;GLU 197;GLU 199;LYS 239
 
1epxDASP 43;LYS 156;GLU 197;GLU 199;LYS 239
 
1ewdAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1ewdBASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1ewdCASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1ewdDASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1eweAASP 33;LYS 146;GLU 187;GLU 189;       
mutant K229M
1eweBASP 33;LYS 146;GLU 187;GLU 189;       
mutant K229M
1eweCASP 33;LYS 146;GLU 187;GLU 189;       
mutant K229M
1eweDASP 33;LYS 146;GLU 187;GLU 189;       
mutant K229M
1ewgAASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187Q
1ewgBASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187Q
1ewgCASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187Q
1ewgDASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187Q
1ex5AASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187A
1ex5BASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187A
1ex5CASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187A
1ex5DASP 33;LYS 146;       ;GLU 189;LYS 229
mutant E187A
1f2jAASP 43;LYS 156;GLU 197;GLU 199;LYS 239
 
1fbaAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1fbaBASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1fbaCASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1fbaDASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1j4eAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1j4eBASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1j4eCASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1j4eDASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5AASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5BASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5CASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5DASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5EASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5FASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5GASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5HASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5IASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5JASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5KASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5LASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5MASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5NASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5OASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5PASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5QASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
1qo5RASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
2aldAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
4aldAASP 33;LYS 146;GLU 187;GLU 189;LYS 229
 
6aldAASP 33;       ;GLU 187;GLU 189;LYS 229
mutant K146A
6aldBASP 33;       ;GLU 187;GLU 189;LYS 229
mutant K146A
6aldCASP 33;       ;GLU 187;GLU 189;LYS 229
mutant K146A
6aldDASP 33;       ;GLU 187;GLU 189;LYS 229
mutant K146A

References for Catalytic Mechanism
ReferencesSectionsNo. 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.38-396
[34]Scheme 1, p.12294, p.12996-129975
[40]p.36-38
[41]Scheme 1, p.2088-20896
[43]p.12662-12663
[45]p.295, Table 3
[46]p.823
[47]p.1149-1150
[51]Fig.5, p.1387410
[54]p.9482

references
[1]
PubMed ID4607364
JournalBiochemistry
Year1974
Volume13
Pages4371-5
AuthorsHeron EJ, Caprioli RM
Title18O studies of the mechanisms of yeast and muscle aldolases.
[2]
PubMed ID954748
JournalEur J Biochem
Year1976
Volume66
Pages95-104
AuthorsLowe G, Pratt RF
TitleProton 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.
[3]
CommentsACTIVE SITE.
Medline ID76190154
PubMed ID5453
JournalJ Biol Chem
Year1976
Volume251
Pages3057-62
AuthorsHartman FC, Brown JP
TitleAffinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase.
Related UniProtKBP00883
[4]
PubMed ID911752
JournalBiochemistry
Year1977
Volume16
Pages3988-94
AuthorsPratt RF
TitleRabbit muscle aldolase catalyzed proton exchange of hydroxyacetone phosphate with solvent.
[5]
PubMed ID18166
JournalBiochemistry
Year1977
Volume16
Pages2966-71
AuthorsStrapazon E, Steck TL
TitleInteraction of the aldolase and the membrane of human erythrocytes.
[6]
PubMed ID540038
JournalBiochem J
Year1979
Volume183
Pages663-7
AuthorsStewart M, Morton DJ, Clarke FM
TitleChanges associated with glycolytic-enzyme binding in the equatorial X-ray-diffraction pattern of glycerinated rabbit psoas muscle.
[7]
CommentsSUBSTRATE-BINDING SITE.
Medline ID80046697
PubMed ID499203
JournalEur J Biochem
Year1979
Volume99
Pages309-13
AuthorsPatthy L, Varadi A, Thesz J, Kovacs K
TitleIdentification of the C-1-phosphate-binding arginine residue of rabbit-muscle aldolase. Isolation of 1,2-cyclohexanedione-labeled peptide by chemisorption chromatography.
Related UniProtKBP00883
[8]
PubMed ID293723
JournalProc Natl Acad Sci U S A
Year1979
Volume76
Pages6323-5
AuthorsPontremoli S, Melloni E, Salamino F, Sparatore B, Michetti M, Horecker BL
TitleChanges in activity of fructose-1,6-bisphosphate aldolase in livers of fasted rabbits and accumulation of crossreacting immune material.
[9]
PubMed ID7385224
JournalTohoku J Exp Med
Year1980
Volume130
Pages143-52
AuthorsNakashima K, Ohtsuki M, Tuboi S
TitleMembrane-bound fructose 1,6-bisphosphate aldolase: catalytic activity and mechanisms of desorption.
[10]
PubMed ID6115420
JournalPhilos Trans R Soc Lond B Biol Sci
Year1981
Volume293
Pages209-14
AuthorsMillar JR, Shaw PJ, Stammers DK, Watson HC
TitleThe low-resolution structure of human muscle aldolase.
[11]
PubMed ID6115413
JournalPhilos Trans R Soc Lond B Biol Sci
Year1981
Volume293
Pages131-43
AuthorsRose IA
TitleChemistry of proton abstraction by glycolytic enzymes (aldolase, isomerases and pyruvate kinase).
[12]
PubMed ID7092833
JournalBiochem J
Year1982
Volume202
Pages589-602
AuthorsBrindle KM, Brown FF, Campbell ID, Foxall DL, Simpson RJ
TitleA 1H n.m.r. study of isotope exchange catalysed by glycolytic enzymes in the human erythrocyte.
[13]
PubMed ID6838539
JournalBiochem Biophys Res Commun
Year1983
Volume110
Pages578-83
AuthorsGrazi E, Trombetta G, Lanzara V
TitleFructose-1,6-bisphosphate-aldolase from rabbit muscle. Half of the sites reactivity at low temperature.
[14]
PubMed ID6679317
JournalBiochem Int
Year1983
Volume6
Pages53-61
AuthorsKelkar SM, Kaklij GS
TitleMechanism of aldolase binding to erythrocyte membrane: Part II. Kinetic aspects.
[15]
PubMed ID6406231
JournalEur J Biochem
Year1983
Volume133
Pages433-7
AuthorsOvadi J, Mohamed Osman IR, Batke J
TitleInteraction of the dissociable glycerol-3-phosphate dehydrogenase and fructose-1,6-bisphosphate aldolase. Quantitative analysis by an extrinsic fluorescence probe.
[16]
PubMed ID6486803
JournalArch Biochem Biophys
Year1984
Volume233
Pages595-602
AuthorsGrazi E, Trombetta G
TitleFructose-1,6-bisphosphate aldolase from rabbit muscle: different catalytic behavior of the dihydroxyacetone phosphate binding sites at low temperature.
[17]
PubMed ID6487321
JournalBiochem Biophys Res Commun
Year1984
Volume123
Pages1069-75
AuthorsSygusch J, Lehoux L, Beaudry D
TitleExtreme X-ray sensitive modification of type I aldolases by blue dye ligand chromatography.
[18]
PubMed ID4026283
JournalAppl Biochem Biotechnol
Year1985
Volume11
Pages91-100
AuthorsAbraham M, Horvath L, Simon M, Szajani B, Boross L
TitleCharacterization and comparison of soluble and immobilized pig muscle aldolases.
[19]
PubMed ID4066671
JournalJ Biol Chem
Year1985
Volume260
Pages15286-90
AuthorsSygusch J, Boulet H, Beaudry D
TitleStructure of rabbit muscle aldolase at low resolution.
[20]
PubMed ID3942758
JournalBiochim Biophys Acta
Year1986
Volume869
Pages185-91
AuthorsSwain MS, Lebherz HG
TitleSpecific, limited tryptic modification of wheat-germ fructose-bisphosphate aldolase subunits: destruction of catalytic activity but not of ability to establish precise subunit-subunit recognition.
[21]
PubMed ID3569280
JournalEur J Biochem
Year1987
Volume164
Pages655-9
AuthorsVertessy B, Ovadi J
TitleA simple approach to detect active-site-directed enzyme-enzyme interactions. The aldolase/glycerol-phosphate-dehydrogenase enzyme system.
[22]
CommentsVARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID88068641
PubMed ID2825199
JournalProc Natl Acad Sci U S A
Year1987
Volume84
Pages8623-7
AuthorsKishi H, Mukai T, Hirono A, Fujii H, Miwa S, Hori K
TitleHuman aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation.
Related UniProtKBP04075
[23]
PubMed ID2556962
JournalAppl Biochem Biotechnol
Year1989
Volume22
Pages223-35
AuthorsHorvath L, Abraham M, Boross L, Szajani B
TitleImmobilization of pig muscle aldolase on a silica-based support.
[24]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID90242948
PubMed ID2335208
JournalFEBS Lett
Year1990
Volume262
Pages282-6
AuthorsGamblin SJ, Cooper B, Millar JR, Davies GJ, Littlechild JA, Watson HC
TitleThe crystal structure of human muscle aldolase at 3.0 A resolution.
Related UniProtKBP04075
[25]
CommentsVARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID91035340
PubMed ID2229018
JournalJ Biochem (Tokyo)
Year1990
Volume108
Pages153-7
AuthorsTakasaki Y, Takahashi I, Mukai T, Hori K
TitleHuman 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 UniProtKBP04075
[26]
PubMed ID1814134
JournalActa Biochim Pol
Year1991
Volume38
Pages407-21
AuthorsKochman M, Dobryszycki P
TitleTopography and conformational changes of fructose-1,6-bisphosphate aldolase.
[27]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID92070498
PubMed ID1959612
JournalFEBS Lett
Year1991
Volume292
Pages237-42
AuthorsHester G, Brenner-Holzach O, Rossi FA, Struck-Donatz M, Winterhalter KH, Smit JD, Piontek K
TitleThe crystal structure of fructose-1,6-bisphosphate aldolase from Drosophila melanogaster at 2.5 A resolution.
Related PDB1fba
Related UniProtKBP07764
[28]
PubMed ID1894606
JournalJ Biol Chem
Year1991
Volume266
Pages17099-105
AuthorsBerthiaume L, Loisel TP, Sygusch J
TitleCarboxyl terminus region modulates catalytic activity of recombinant maize aldolase.
[29]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID91278081
PubMed ID2056525
JournalJ Mol Biol
Year1991
Volume219
Pages573-6
AuthorsGamblin SJ, Davies GJ, Grimes JM, Jackson RM, Littlechild JA, Watson HC
TitleActivity and specificity of human aldolases.
Related PDB1ald
Related UniProtKBP04075
[30]
PubMed ID1417758
JournalBiochem J
Year1992
Volume286
Pages977-9
AuthorsVertessy BG, Vas M
TitleMetabolite channeling versus free diffusion: reinterpretation of aldolase-catalysed inactivation of glyceraldehyde-3-phosphate dehydrogenase.
[31]
PubMed ID1577806
JournalJ Biol Chem
Year1992
Volume267
Pages9713-7
AuthorsRae C, Bubb WA, Kuchel PW
TitleAldolase-catalyzed diketone phosphate formation from oxoaldehydes. NMR studies and metabolic significance.
[32]
PubMed ID8513801
JournalEur J Biochem
Year1993
Volume214
Pages515-9
AuthorsGupta S, Hollenstein R, Kochhar S, Christen P
TitleParacatalytic self-inactivation of fructose-1,6-bisphosphate aldolase. Structure of the crosslink formed at the active site.
[33]
PubMed ID8488556
JournalTrends Biochem Sci
Year1993
Volume18
Pages36-9
AuthorsLittlechild JA, Watson HC
TitleA data-based reaction mechanism for type I fructose bisphosphate aldolase.
[34]
PubMed ID7918450
JournalBiochemistry
Year1994
Volume33
Pages12291-7
AuthorsMorris AJ, Tolan DR
TitleLysine-146 of rabbit muscle aldolase is essential for cleavage and condensation of the C3-C4 bond of fructose 1,6-bis(phosphate).
[35]
PubMed ID8527430
JournalBiochemistry
Year1995
Volume34
Pages16574-84
AuthorsSchneider ML, Post CB
TitleSolution structure of a band 3 peptide inhibitor bound to aldolase: a proposed mechanism for regulating binding by tyrosine phosphorylation.
[36]
PubMed ID8636111
JournalJ Biol Chem
Year1996
Volume271
Pages6861-5
AuthorsWang J, Morris AJ, Tolan DR, Pagliaro L
TitleThe molecular nature of the F-actin binding activity of aldolase revealed with site-directed mutants.
[37]
PubMed ID8643582
JournalProc Natl Acad Sci U S A
Year1996
Volume93
Pages5374-9
AuthorsBeernink PT, Tolan DR
TitleDisruption of the aldolase A tetramer into catalytically active monomers.
[38]
CommentsX-ray crystallography
JournalProtein Pept Lett
Year1996
Volume3
Pages207-12
AuthorsDalby A, Rawas A, Watson HC, Littlechild JA
TitleCrystallisation and Preliminary X-Ray Diffraction Studies on Human Liver Aldolase.
Related PDB1qo5
[39]
PubMed ID9325270
JournalJ Biol Chem
Year1997
Volume272
Pages25542-6
AuthorsVertessy BG, Orosz F, Kovacs J, Ovadi J
TitleAlternative binding of two sequential glycolytic enzymes to microtubules. Molecular studies in the phosphofructokinase/aldolase/microtubule system.
[40]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID97143309
PubMed ID8989320
JournalNat Struct Biol
Year1997
Volume4
Pages36-9
AuthorsBlom N, Sygusch J
TitleProduct binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase.
Related PDB1ado
Related UniProtKBP00883
[41]
PubMed ID9405338
JournalScience
Year1997
Volume278
Pages2085-92
AuthorsBarbas CF 3rd, Heine A, Zhong G, Hoffmann T, Gramatikova S, Bjornestedt R, List B, Anderson J, Stura EA, Wilson IA, Lerner RA
TitleImmune versus natural selection: antibody aldolases with enzymic rates but broader scope.
[42]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
Medline ID98190013
PubMed ID9521758
JournalBiochemistry
Year1998
Volume37
Pages4388-96
AuthorsKim H, Certa U, Dobeli H, Jakob P, Hol WG
TitleCrystal structure of fructose-1,6-bisphosphate aldolase from the human malaria parasite Plasmodium falciparum.
Related PDB1a5c
Related UniProtKBP14223
[43]
CommentsX-ray crystallography
PubMed ID10504235
JournalBiochemistry
Year1999
Volume38
Pages12655-64
AuthorsChoi KH, Mazurkie AS, Morris AJ, Utheza D, Tolan DR, Allen KN
TitleStructure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 A(,).
Related PDB6ald
[44]
PubMed ID10336621
JournalEur J Biochem
Year1999
Volume262
Pages371-6
AuthorsPettersson H, Pettersson G
TitleMechanism of metabolite transfer in coupled two-enzyme reactions involving aldolase.
[45]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID99156067
PubMed ID10048322
JournalProtein Sci
Year1999
Volume8
Pages291-7
AuthorsDalby A, Dauter Z, Littlechild JA
TitleCrystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: mechanistic implications.
Related PDB2ald,4ald
Related UniProtKBP04075
[46]
PubMed ID10970798
JournalBiochem J
Year2000
Volume350 Pt 3
Pages823-8
AuthorsSantamaria R, Esposito G, Vitagliano L, Race V, Paglionico I, Zancan L, Zagari A, Salvatore F
TitleFunctional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase.
[47]
PubMed ID10625657
JournalJ Biol Chem
Year2000
Volume275
Pages1145-51
AuthorsRellos P, Sygusch J, Cox TM
TitleExpression, purification, and characterization of natural mutants of human aldolase B. Role of quaternary structure in catalysis.
[48]
CommentsX-ray crystallography
PubMed ID10891264
JournalJ Mol Biol
Year2000
Volume300
Pages697-707
AuthorsChudzik DM, Michels PA, de Walque S, Hol WG
TitleStructures of type 2 peroxisomal targeting signals in two trypanosomatid aldolases.
Related PDB1epx,1f2j
Related UniProtKBP07752
[49]
PubMed ID10959854
JournalJ Org Chem
Year2000
Volume65
Pages4529-31
AuthorsChenevert R, Dasser M
TitleChemoenzymatic synthesis of the microbial elicitor (-)-syringolide via a fructose 1,6-diphosphate aldolase-catalyzed condensation reaction.
[50]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS)
PubMed ID11679716
JournalActa Crystallogr D Biol Crystallogr
Year2001
Volume57
Pages1526-33
AuthorsDalby AR, Tolan DR, Littlechild JA
TitleThe structure of human liver fructose-1,6-bisphosphate aldolase.
Related UniProtKBP05062
[51]
PubMed ID11705376
JournalBiochemistry
Year2001
Volume40
Pages13868-75
AuthorsChoi KH, Shi J, Hopkins CE, Tolan DR, Allen KN
TitleSnapshots of catalysis: the structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate.
Related PDB1j4e
[52]
PubMed ID11371431
JournalBiophys J
Year2001
Volume80
Pages2527-35
AuthorsOuporov IV, Knull HR, Huber A, Thomasson KA
TitleBrownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling.
[53]
PubMed ID12417303
JournalFEBS Lett
Year2002
Volume531
Pages152-6
AuthorsEsposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F
TitleStructural and functional analysis of aldolase B mutants related to hereditary fructose intolerance.
[54]
CommentsX-ray crystallography
PubMed ID11779856
JournalJ Biol Chem
Year2002
Volume277
Pages9474-83
AuthorsMaurady A, Zdanov A, de Moissac D, Beaudry D, Sygusch J
TitleA conserved glutamate residue exhibits multifunctional catalytic roles in D-fructose-1,6-bisphosphate aldolases.
Related PDB1ewd,1ewe,1ewg,1ex5
[55]
PubMed ID11835505
JournalProteins
Year2002
Volume46
Pages295-307
AuthorsZabell AP, Post CB
TitleDocking multiple conformations of a flexible ligand into a protein binding site using NMR restraints.
[56]
PubMed ID15025449
JournalJ Am Chem Soc
Year2004
Volume126
Pages3402-3
AuthorsChoi KH, Tolan DR
TitlePresteady-state kinetic evidence for a ring-opening activity in fructose-1,6-(bis)phosphate aldolase.

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.

createdupdated
2004-05-242009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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