EzCatDB: S00199

DB codeS00199
RLCP classification6.10.400600.113
5.121.671000.6111
8.112.3600000.6580
6.20.7800.6111
CATH domainDomain 13.20.20.70Catalytic domain
E.C.4.1.2.13
CSA1ald

CATH domainRelated DB codes (homologues)
3.20.20.70S00215,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
Swiss-protKEGG

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

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

Swiss-prot: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







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
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

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Related Swiss-protP00883
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Year1983
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Year1984
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Year1987
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[22]
CommentsVARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID88068641
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Related Swiss-protP04075
[23]
PubMed ID2556962
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Year1989
Volume22
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[24]
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Medline ID90242948
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Year1990
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Related Swiss-protP04075
[25]
CommentsVARIANT HEMOLYTIC ANEMIA GLY-128.
Medline ID91035340
PubMed ID2229018
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Year1990
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Related Swiss-protP04075
[26]
PubMed ID1814134
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Year1991
Volume38
Pages407-21
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Medline ID92070498
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Related PDB1fba
Related Swiss-protP07764
[28]
PubMed ID1894606
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Year1991
Volume266
Pages17099-105
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Medline ID91278081
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Related PDB1ald
Related Swiss-protP04075
[30]
PubMed ID1417758
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Year1992
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Year1992
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Year1993
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[34]
PubMed ID7918450
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Year1994
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Year1995
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[36]
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Year1996
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Year1996
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[38]
CommentsX-ray crystallography
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Year1996
Volume3
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Related PDB1qo5
[39]
PubMed ID9325270
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Year1997
Volume272
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CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID97143309
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Year1997
Volume4
Pages36-9
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Related PDB1ado
Related Swiss-protP00883
[41]
PubMed ID9405338
JournalScience
Year1997
Volume278
Pages2085-92
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[42]
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Related PDB1a5c
Related Swiss-protP14223
[43]
CommentsX-ray crystallography
PubMed ID10504235
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Year1999
Volume38
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Related PDB6ald
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PubMed ID10336621
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Medline ID99156067
PubMed ID10048322
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Year1999
Volume8
Pages291-7
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Related PDB2ald,4ald
Related Swiss-protP04075
[46]
PubMed ID10970798
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Year2000
Volume350 Pt 3
Pages823-8
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[47]
PubMed ID10625657
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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 Swiss-protP07752
[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 Swiss-protP05062
[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 2010)
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)

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