Transaldolase
Identifiers
EC no.2.2.1.2
CAS no.9014-46-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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PMCarticles
PubMedarticles
NCBIproteins
Transaldolase
Crystallographic structure of human transaldolase.[1][2]
Identifiers
SymbolTransaldolase
PfamPF00923
InterProIPR001585
PROSITEPDOC00741
SCOP21ucw / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1f05​, 1i2n​, 1i2o​, 1i2p​, 1i2q​, 1i2r​, 1l6w​, 1onr​, 1ucw​,1vpx​, 2cwn​
transaldolase 1
Identifiers
SymbolTALDO1
NCBI gene6888
HGNC11559
OMIM602063
RefSeqNM_006755
UniProtP37837
Other data
EC number2.2.1.2
LocusChr. 11 p15.5-15.4
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StructuresSwiss-model
DomainsInterPro
transaldolase B
Identifiers
SymboltalB
NCBI gene4199095
PDB1onr
RefSeqNC_008245.1
UniProtP0A870
Other data
EC number2.2.1.2
Search for
StructuresSwiss-model
DomainsInterPro

Transaldolase is an enzyme (EC 2.2.1.2) of the non-oxidative phase of the pentose phosphate pathway. In humans, transaldolase is encoded by the TALDO1 gene.[3][4]

The following chemical reaction is catalyzed by transaldolase:

sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate erythrose 4-phosphate + fructose 6-phosphate

Clinical significance

The pentose phosphate pathway has two metabolic functions: (1) generation of nicotinamide adenine dinucleotide phosphate (reduced NADPH), for reductive biosynthesis, and (2) formation of ribose, which is an essential component of ATP, DNA, and RNA. Transaldolase links the pentose phosphate pathway to glycolysis. In patients with deficiency of transaldolase, there's an accumulation of erythritol (from erythrose 4-phosphate), D-arabitol, and ribitol.[5][6]

The deletion in 3 base pairs in the TALDO1 gene results in the absence of serine at position 171 of the transaldolase protein, which is part of a highly conserved region, suggesting that the mutation causes the transaldolase deficiency that is found in erythrocytes and lymphoblasts.[5] The deletion of this amino acid can lead to liver cirrhosis and hepatosplenomegaly (enlarged spleen and liver) during early infancy. Transaldolase is also a target of autoimmunity in patients with multiple sclerosis.[7]

Structure

Active site of the transaldolase enzyme highlighting the key amino acid residues (Asp-27, Glu-106, and Lys-142) involved in catalysis.[1]

Transaldolase is a single domain composed of 337 amino acids. The core structure is an α/β barrel, similar to other class I aldolases, made up of eight parallel β-sheets and seven α-helices. There are also seven additional α-helices that are not part of the barrel. Hydrophobic amino acids are located between the β-sheets in the barrel and the surrounding α-helices to contribute to packing, such as the area containing Leu-168, Phe-170, Phe-189, Gly-311, and Phe-315. In the crystal, human transaldolase forms a dimer, with the two subunits connected by 18 residues in each subunit. See mechanism to the left for details.

The active site, located in the center of the barrel, contains three key residues: lysine-142, glutamate-106, and aspartate-27. The lysine holds the sugar in place while the glutamate and aspartate act as proton donors and acceptors.[1]

Mechanism of catalysis

The residue of lysine-142 in the active site of transaldolase forms a Schiff base with the keto group in sedoheptulose-7-phosphate after deprotonation by another active site residue, glutamate-106. The reaction mechanism is similar to the reverse reaction catalyzed by aldolase: The bond joining carbons 3 and 4 is broken, leaving dihydroxyacetone joined to the enzyme via a Schiff base. This cleavage reaction generates the unusual aldose sugar erythrose-4-phosphate. Then transaldolase catalyzes the condensation of glyceraldehyde-3-phosphate with the Schiff base of dihydroxyacetone, yielding enzyme-bound fructose 6-phosphate. Hydrolysis of the Schiff base liberates free fructose 6-phosphate, one of the products of the pentose phosphate pathway.

See also

References

  1. 1 2 3 PDB: 1F05​; Thorell S, Gergely P, Banki K, Perl A, Schneider G (June 2000). "The three-dimensional structure of human transaldolase". FEBS Lett. 475 (3): 205–8. doi:10.1016/S0014-5793(00)01658-6. PMID 10869557. S2CID 33590067.
  2. ↑ Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (October 2004). "UCSF Chimera–a visualization system for exploratory research and analysis". J Comput Chem. 25 (13): 1605–12. CiteSeerX 10.1.1.456.9442. doi:10.1002/jcc.20084. PMID 15264254. S2CID 8747218.
  3. ↑ "Entrez Gene: transaldolase 1".
  4. ↑ Banki K, Eddy RL, Shows TB, Halladay DL, Bullrich F, Croce CM, Jurecic V, Baldini A, Perl A (October 1997). "The human transaldolase gene (TALDO1) is located on chromosome 11 at p15.4-p15.5". Genomics. 45 (1): 233–8. doi:10.1006/geno.1997.4932. PMID 9339383.
  5. 1 2 3 Verhoeven NM, Huck JH, Roos B, Struys EA, Salomons GS, Douwes AC, van der Knaap MS, Jakobs C (May 2001). "Transaldolase deficiency: liver cirrhosis associated with a new inborn error in the pentose phosphate pathway". Am. J. Hum. Genet. 68 (5): 1086–92. doi:10.1086/320108. PMC 1226089. PMID 11283793.
  6. ↑ Perl A (June 2007). "The pathogenesis of transaldolase deficiency". IUBMB Life. 59 (6): 365–73. doi:10.1080/15216540701387188. PMID 17613166. S2CID 10428599.
  7. ↑ Niland B, Perl A (2004). "Evaluation of autoimmunity to transaldolase in multiple sclerosis". Autoimmunity. Vol. 102. pp. 155–71. doi:10.1385/1-59259-805-6:155. ISBN 978-1-59259-805-2. PMID 15286385. {{cite book}}: |journal= ignored (help)
  8. ↑ Jia J, Schörken U, Lindqvist Y, Sprenger GA, Schneider G (January 1997). "Crystal structure of the reduced Schiff-base intermediate complex of transaldolase B from Escherichia coli: mechanistic implications for class I aldolases". Protein Sci. 6 (1): 119–24. doi:10.1002/pro.5560060113. PMC 2143518. PMID 9007983.
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