DB code: S00198

RLCP classification	6.10.400000.116 : Double-bonded atom exchange
	5.121.670200.6100 : Elimination
	4.121.143000.6100 : Addition
	6.20.7100.6120 : Double-bonded atom exchange
CATH domain	3.20.20.70 : TIM Barrel	Catalytic domain
E.C.	2.2.1.2
CSA	1onr
M-CSA	1onr
MACiE	M0148

CATH domain	Related DB codes (homologues)
3.20.20.70 : TIM Barrel	S00215 S00217 S00218 S00219 S00532 S00220 S00745 S00537 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00199 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
P0A870	Transaldolase B	EC 2.2.1.2	NP_414549.1 (Protein) NC_000913.2 (DNA/RNA sequence) YP_488314.1 (Protein) NC_007779.1 (DNA/RNA sequence)	PF00923 (Transaldolase) [Graphical View]
P37837	Transaldolase	EC 2.2.1.2	NP_006746.1 (Protein) NM_006755.1 (DNA/RNA sequence)	PF00923 (Transaldolase) [Graphical View]

KEGG enzyme name
transaldolase dihydroxyacetonetransferase dihydroxyacetone synthase formaldehyde transketolase

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P0A870	TALB_ECOLI	Sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-erythrose 4-phosphate + D-fructose 6-phosphate.	Homodimer.	Cytoplasm (Probable).
P37837	TALDO_HUMAN	Sedoheptulose 7-phosphate + D-glyceraldehyde 3-phosphate = D-erythrose 4-phosphate + D-fructose 6-phosphate.		Cytoplasm (Probable).

KEGG Pathways
Map code	Pathways	E.C.
MAP00030	Pentose phosphate pathway

Compound table
	Substrates		Products		Intermediates
KEGG-id	C00085	C00279	C00118	C00281
E.C.					(1st intermediate)
Compound	D-Fructose 6-phosphate	D-Erythrose 4-phosphate	D-Glyceraldehyde 3-phosphate	Sedoheptulose 7-phosphate	Schiff-base intermediate
Type	carbohydrate,phosphate group/phosphate ion	carbohydrate,phosphate group/phosphate ion	carbohydrate,phosphate group/phosphate ion	carbohydrate,phosphate group/phosphate ion
ChEBI	61553 61553	48153 48153	29052 29052
PubChem	439160 439160	122357 122357	439168 439168

1f05A	Unbound	Unbound	Unbound	Unbound	Unbound
1f05B	Unbound	Unbound	Unbound	Unbound	Unbound
1i2nA	Unbound	Unbound	Unbound	Unbound	Unbound
1i2nB	Unbound	Unbound	Unbound	Unbound	Unbound
1i2oA	Unbound	Unbound	Unbound	Unbound	Unbound
1i2oB	Unbound	Unbound	Unbound	Unbound	Unbound
1i2pA	Unbound	Unbound	Unbound	Unbound	Unbound
1i2pB	Unbound	Unbound	Unbound	Unbound	Unbound
1i2qA	Unbound	Unbound	Unbound	Unbound	Unbound
1i2qB	Unbound	Unbound	Unbound	Unbound	Unbound
1i2rA	Unbound	Unbound	Unbound	Unbound	Unbound
1i2rB	Unbound	Unbound	Unbound	Unbound	Unbound
1onrA	Unbound	Unbound	Unbound	Unbound	Unbound
1onrB	Unbound	Unbound	Unbound	Unbound	Unbound
1ucwA	Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:LLY
1ucwB	Unbound	Unbound	Unbound	Unbound	Intermediate-analogue:LLY

Reference for Active-site residues
resource	references	E.C.
Swiss-prot;P30148, P37837 & literature [7], [9], [10], [12], [17]

Active-site residues
PDB	Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment

1f05A	ASP 27;GLU 106;LYS 142;THR 167
1f05B	ASP 27;GLU 106;LYS 142;THR 167
1i2nA	ASP 17;GLU 96;LYS 132;THR 156				mutant N35A
1i2nB	ASP 17;GLU 96;LYS 132;THR 156				mutant N35A
1i2oA	ASP 17; ;LYS 132;THR 156				mutant E96A
1i2oB	ASP 17; ;LYS 132;THR 156				mutant E96A
1i2pA	;GLU 96;LYS 132;THR 156				mutant D17A
1i2pB	;GLU 96;LYS 132;THR 156				mutant D17A
1i2qA	ASP 17;GLU 96;LYS 132;				mutant T156A
1i2qB	ASP 17;GLU 96;LYS 132;				mutant T156A
1i2rA	ASP 17;GLU 96;LYS 132;THR 156				mutant S176A
1i2rB	ASP 17;GLU 96;LYS 132;THR 156				mutant S176A
1onrA	ASP 17;GLU 96;LYS 132;THR 156
1onrB	ASP 17;GLU 96;LYS 132;THR 156
1ucwA	ASP 17;GLU 96;LLY 132;THR 156		LLY 132(modified with reduced schiff-base intermediate)
1ucwB	ASP 17;GLU 96;LLY 132;THR 156		LLY 132(modified with reduced schiff-base intermediate)

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[10]	Fig.5, p.721
[11]	p.305
[12]	Fig.5, p.122
[14]	p.294-295
[17]	Fig.4, p.2412-2414

References
[1]
Resource
Comments
Medline ID
PubMed ID	4799825
Journal	Biochemistry
Year	1973
Volume	12
Pages	5217-23
Authors	Kuhn E, Brand K
Title	Computer analysis of the two-substrate reaction catalyzed by yeast and bovine transaldolase
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID	945040
Journal	Arch Biochem Biophys
Year	1976
Volume	173
Pages	577-85
Authors	Tsolas O, Horecker BL
Title	Half-of-the-sites activity of transaldolase
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID	776982
Journal	J Biol Chem
Year	1976
Volume	251
Pages	4220-3
Authors	Christen P, Gasser A
Title	Oxidation of the carbanion intermediate of transaldolase by hexacyanoferrate (III)
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID	728110
Journal	Biochem J
Year	1978
Volume	176
Pages	257-82
Authors	Williams JF, Blackmore PF, Clark MG
Title	New reaction sequences for the non-oxidative pentose phosphate pathway
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	8357848
Journal	Biochim Biophys Acta
Year	1993
Volume	1182
Pages	162-78
Authors	Schrader MC, Eskey CJ, Simplaceanu V, Ho C
Title	A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated with glucose metabolism in human erythrocytes
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	8477719
Journal	Eur J Biochem
Year	1993
Volume	213
Pages	477-85
Authors	Flanigan I, Collins JG, Arora KK, MacLeod JK, Williams JF
Title	Exchange reactions catalyzed by group-transferring enzymes oppose the quantitation and the unravelling of the identify of the pentose pathway
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	8109173
Journal	Yeast
Year	1993
Volume	9
Pages	1241-9
Authors	Miosga T, Schaaff-Gerstenschlager I, Franken E, Zimmermann FK
Title	Lysine144 is essential for the catalytic activity of Saccharomyces cerevisiae transaldolase
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	8534086
Journal	Appl Environ Microbiol
Year	1995
Volume	61
Pages	4184-90
Authors	Walfridsson M, Hallborn J, Penttila M, Keranen S, Hahn-Hagerdal B
Title	Xylose-metabolizing Saccharomyces cerevisiae strains overexpressing the TKL1 and TAL1 genes encoding the pentose phosphate pathway enzymes transketolase and transaldolase
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	8549825
Journal	FEBS Lett
Year	1996
Volume	378
Pages	161-5
Authors	Banki K, Perl A
Title	Inhibition of the catalytic activity of human transaldolase by antibodies and site-directed mutagenesis
Related PDB
Related UniProtKB
[10]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS).
Medline ID	96399717
PubMed ID	8805555
Journal	Structure
Year	1996
Volume	4
Pages	715-24
Authors	Jia J, Huang W, Schorken U, Sahm H, Sprenger GA, Lindqvist Y, Schneider G
Title	Crystal structure of transaldolase B from Escherichia coli suggests a circular permutation of the alpha/beta barrel within the class I aldolase family
Related PDB	1onr
Related UniProtKB	P30148
[11]
Resource
Comments
Medline ID
PubMed ID	9343352
Journal	Annu Rev Microbiol
Year	1997
Volume	51
Pages	285-310
Authors	Takayama S, McGarvey GJ, Wong CH
Title	Microbial aldolases and transketolases
Related PDB
Related UniProtKB
[12]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID	97160483
PubMed ID	9007983
Journal	Protein Sci
Year	1997
Volume	6
Pages	119-24
Authors	Jia J, Schorken U, Lindqvist Y, Sprenger GA, Schneider G
Title	Crystal structure of the reduced Schiff-base intermediate complex of transaldolase B from Escherichia coli
Related PDB	1ucw
Related UniProtKB	P30148
[13]
Resource
Comments
Medline ID
PubMed ID	9883893
Journal	FEBS Lett
Year	1998
Volume	441
Pages	247-50
Authors	Schorken U, Jia J, Sahm H, Sprenger GA, Schneider G
Title	Disruption of Escherichia coli transaldolase into catalytically active monomers
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
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
Related PDB
Related UniProtKB
[15]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	10869557
Journal	FEBS Lett
Year	2000
Volume	475
Pages	205-8
Authors	Thorell S, Gergely P Jr, Banki K, Perl A, Schneider G
Title	The three-dimensional structure of human transaldolase
Related PDB	1f05
Related UniProtKB
[16]
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
Related PDB
Related UniProtKB
[17]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
Medline ID	21195256
PubMed ID	11298760
Journal	Eur J Biochem
Year	2001
Volume	268
Pages	2408-15
Authors	Schorken U, Thorell S, Schurmann M, Jia J, Sprenger GA, Schneider G
Title	Identification of catalytically important residues in the active site of Escherichia coli transaldolase
Related PDB	1i2n 1i2o 1i2p 1i2q 1i2r
Related UniProtKB	P30148
[18]
Resource
Comments
Medline ID
PubMed ID	11120740
Journal	J Biol Chem
Year	2001
Volume	276
Pages	11055-61
Authors	Schurmann M, Sprenger GA
Title	Fructose-6-phosphate aldolase is a novel class I aldolase from Escherichia coli and is related to a novel group of bacterial transaldolases
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID	12418227
Journal	Methods Enzymol
Year	2002
Volume	354
Pages	197-201
Authors	Schneider G, Sprenger GA
Title	Transaldolase B: trapping of Schiff base intermediate between dihydroxyacetone and epsilon-amino group of active-site lysine residue by borohydride reduction.
Related PDB
Related UniProtKB

Comments
According to the literature [10], [12] & [17], the catalytic reactions of this enzyme proceed as follows: (A) Exchange of double-bonded atoms; Schiff-base formation: (A1) Glu96 (PDB;1onr) acts as a general base to abstract a proton from the sidechain of Lys132 through a water, enhancing its nucleophilicity. This water is oriented by Thr156. (A2) The activated Lys132 makes a nucleophilic attack on C2-carbonyl carbon, to form a carbinolamine intermediate. The negative charge developed on the C2-oxygen of the intermediate is stabilized by interaction with Thr156. (Here, a proton must transfer from the sidechain amine of Lys132 to the C2-carbonyl oxygen, with a probable assistance by the same water. The water may protonate the C2-carbonyl oxygen, and then deprotonate the amine of Lys132.) (A3) The lone pair of Lys132 makes another attak on C2-carbon, whilst Glu96 acts as a general acid to protonate the leaving hydroxyl group through the same water. This reaction leads to Schiff-base intermeidate formation. (B) Eliminative double-bond formation;C3-C4 bond cleavage: (B1) Glu17 acts as a general base to deprotonate C4-hydroxyl group, leading to the C3-C4 bond cleavage (E2-like reaction). This reaction leads to the formation of carbanion at C2 atom, and the release of the first product, G3P. (B2) The negative charge formed at C2 facilitates the formation of C2=C3 double-bond, or ketamine (or enamine) intermediate. (C) Additive double-bond deformation; Addition of the second substrate (E4P): (C1) The C3 atom of the enamine intemediate makes a nucleophilic attack on the carbonyl carbon of the second substrate, E4P. (C2) Asp17 acts as a general acid to protonate the aldehyde oxygen of E4P, facilitating the nucleophilic attack of the enamine on E4P. This reaction leads to the Schiff base at Lys132 again. (D) Exchange of double-bonded atoms; Schiff-base deformation: (D1) A water molecule is activated by a general base, Glu96, through a second water. (D2) The activated water makes a nucleophilic attack on the Schiff base carbon, to form a carbinolamine intermediate. The negative charge developed on the C2-oxygen of the intermediate is stabilized by interaction with Thr156. (Here, a proton must transfer from the C2-hydroxylg group to the sidechain amine of Lys132, with a probable assistance by the same water. The water may deprotonate the C2-hydroxyl oxygen, and then protonate the amine of Lys132.) (D3) The lone pair of the C2-oxygen makes a nucleophilic attack on the C2 atom, whilst Glu96 acts as a general acid to protonate the leaving Lys132 amine group through the same water. This reaction leads to release of the product.

Comments

According to the literature [10], [12] & [17], the catalytic reactions of this enzyme proceed as follows:
(A) Exchange of double-bonded atoms; Schiff-base formation:
(A1) Glu96 (PDB;1onr) acts as a general base to abstract a proton from the sidechain of Lys132 through a water, enhancing its nucleophilicity. This water is oriented by Thr156.
(A2) The activated Lys132 makes a nucleophilic attack on C2-carbonyl carbon, to form a carbinolamine intermediate. The negative charge developed on the C2-oxygen of the intermediate is stabilized by interaction with Thr156. (Here, a proton must transfer from the sidechain amine of Lys132 to the C2-carbonyl oxygen, with a probable assistance by the same water. The water may protonate the C2-carbonyl oxygen, and then deprotonate the amine of Lys132.)
(A3) The lone pair of Lys132 makes another attak on C2-carbon, whilst Glu96 acts as a general acid to protonate the leaving hydroxyl group through the same water. This reaction leads to Schiff-base intermeidate formation.
(B) Eliminative double-bond formation;C3-C4 bond cleavage:
(B1) Glu17 acts as a general base to deprotonate C4-hydroxyl group, leading to the C3-C4 bond cleavage (E2-like reaction). This reaction leads to the formation of carbanion at C2 atom, and the release of the first product, G3P.
(B2) The negative charge formed at C2 facilitates the formation of C2=C3 double-bond, or ketamine (or enamine) intermediate.
(C) Additive double-bond deformation; Addition of the second substrate (E4P):
(C1) The C3 atom of the enamine intemediate makes a nucleophilic attack on the carbonyl carbon of the second substrate, E4P.
(C2) Asp17 acts as a general acid to protonate the aldehyde oxygen of E4P, facilitating the nucleophilic attack of the enamine on E4P. This reaction leads to the Schiff base at Lys132 again.
(D) Exchange of double-bonded atoms; Schiff-base deformation:
(D1) A water molecule is activated by a general base, Glu96, through a second water.
(D2) The activated water makes a nucleophilic attack on the Schiff base carbon, to form a carbinolamine intermediate. The negative charge developed on the C2-oxygen of the intermediate is stabilized by interaction with Thr156. (Here, a proton must transfer from the C2-hydroxylg group to the sidechain amine of Lys132, with a probable assistance by the same water. The water may deprotonate the C2-hydroxyl oxygen, and then protonate the amine of Lys132.)
(D3) The lone pair of the C2-oxygen makes a nucleophilic attack on the C2 atom, whilst Glu96 acts as a general acid to protonate the leaving Lys132 amine group through the same water. This reaction leads to release of the product.

Created	Updated
2005-03-25	2009-03-11