Transaldolase

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Transaldolase
Identifiers
EC no. 2.2.1.2
CAS no. 9014-46-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
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PMC articles
PubMed articles
NCBI proteins
Transaldolase
Transaldolaseribbon.jpg
Crystallographic structure of human transaldolase. [1] [2]
Identifiers
SymbolTransaldolase
Pfam PF00923
InterPro IPR001585
PROSITE PDOC00741
SCOP2 1ucw / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1f05 , 1i2n , 1i2o , 1i2p , 1i2q , 1i2r , 1l6w , 1onr , 1ucw , 1vpx , 2cwn
transaldolase 1
Identifiers
SymbolTALDO1
NCBI gene 6888
HGNC 11559
OMIM 602063
RefSeq NM_006755
UniProt P37837
Other data
EC number 2.2.1.2
Locus Chr. 11 p15.5-15.4
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Structures Swiss-model
Domains InterPro
transaldolase B
Identifiers
SymboltalB
NCBI gene 4199095
PDB 1onr
RefSeq NC_008245.1
UniProt P0A870
Other data
EC number 2.2.1.2
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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

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

Related Research Articles

In organic chemistry, a tetrose is a monosaccharide with 4 carbon atoms. They have either an aldehyde functional group in position 1 (aldotetroses) or a ketone group in position 2 (ketotetroses).

<span class="mw-page-title-main">Pyridoxal phosphate</span> Active form of vitamin B6

Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

<span class="mw-page-title-main">Calvin cycle</span> Light-independent reactions in photosynthesis

The Calvin cycle, light-independent reactions, bio synthetic phase, dark reactions, or photosynthetic carbon reduction (PCR) cycle of photosynthesis is a series of chemical reactions that convert carbon dioxide and hydrogen-carrier compounds into glucose. The Calvin cycle is present in all photosynthetic eukaryotes and also many photosynthetic bacteria. In plants, these reactions occur in the stroma, the fluid-filled region of a chloroplast outside the thylakoid membranes. These reactions take the products of light-dependent reactions and perform further chemical processes on them. The Calvin cycle uses the chemical energy of ATP and reducing power of NADPH from the light dependent reactions to produce sugars for the plant to use. These substrates are used in a series of reduction-oxidation (redox) reactions to produce sugars in a step-wise process; there is no direct reaction that converts several molecules of CO2 to a sugar. There are three phases to the light-independent reactions, collectively called the Calvin cycle: carboxylation, reduction reactions, and ribulose 1,5-bisphosphate (RuBP) regeneration.

<span class="mw-page-title-main">Glyceraldehyde 3-phosphate</span> Chemical compound

Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GA3P, GADP, GAP, TP, GALP or PGAL, is a metabolite that occurs as an intermediate in several central pathways of all organisms. With the chemical formula H(O)CCH(OH)CH2OPO32-, this anion is a monophosphate ester of glyceraldehyde.

<span class="mw-page-title-main">Aldolase A</span> Mammalian protein found in Homo sapiens

Aldolase A, also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ALDOA gene on chromosome 16.

Dihydroxyacetone phosphate (DHAP, also glycerone phosphate in older texts) is the anion with the formula HOCH2C(O)CH2OPO32-. This anion is involved in many metabolic pathways, including the Calvin cycle in plants and glycolysis. It is the phosphate ester of dihydroxyacetone.

<span class="mw-page-title-main">Triosephosphate isomerase</span> Enzyme involved in glycolysis

Triose-phosphate isomerase is an enzyme that catalyzes the reversible interconversion of the triose phosphate isomers dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate.

<span class="mw-page-title-main">Transketolase</span> Enzyme involved in metabolic pathways

Transketolase is an enzyme that, in humans, is encoded by the TKT gene. It participates in both the pentose phosphate pathway in all organisms and the Calvin cycle of photosynthesis. Transketolase catalyzes two important reactions, which operate in opposite directions in these two pathways. In the first reaction of the non-oxidative pentose phosphate pathway, the cofactor thiamine diphosphate accepts a 2-carbon fragment from a 5-carbon ketose (D-xylulose-5-P), then transfers this fragment to a 5-carbon aldose (D-ribose-5-P) to form a 7-carbon ketose (sedoheptulose-7-P). The abstraction of two carbons from D-xylulose-5-P yields the 3-carbon aldose glyceraldehyde-3-P. In the Calvin cycle, transketolase catalyzes the reverse reaction, the conversion of sedoheptulose-7-P and glyceraldehyde-3-P to pentoses, the aldose D-ribose-5-P and the ketose D-xylulose-5-P.

<span class="mw-page-title-main">Aldolase B</span> Mammalian protein found in Homo sapiens

Aldolase B also known as fructose-bisphosphate aldolase B or liver-type aldolase is one of three isoenzymes of the class I fructose 1,6-bisphosphate aldolase enzyme, and plays a key role in both glycolysis and gluconeogenesis. The generic fructose 1,6-bisphosphate aldolase enzyme catalyzes the reversible cleavage of fructose 1,6-bisphosphate (FBP) into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP) as well as the reversible cleavage of fructose 1-phosphate (F1P) into glyceraldehyde and dihydroxyacetone phosphate. In mammals, aldolase B is preferentially expressed in the liver, while aldolase A is expressed in muscle and erythrocytes and aldolase C is expressed in the brain. Slight differences in isozyme structure result in different activities for the two substrate molecules: FBP and fructose 1-phosphate. Aldolase B exhibits no preference and thus catalyzes both reactions, while aldolases A and C prefer FBP.

<span class="mw-page-title-main">Erythrose 4-phosphate</span> Chemical compound

Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle.

<span class="mw-page-title-main">Fructose-bisphosphate aldolase</span>

Fructose-bisphosphate aldolase, often just aldolase, is an enzyme catalyzing a reversible reaction that splits the aldol, fructose 1,6-bisphosphate, into the triose phosphates dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). Aldolase can also produce DHAP from other (3S,4R)-ketose 1-phosphates such as fructose 1-phosphate and sedoheptulose 1,7-bisphosphate. Gluconeogenesis and the Calvin cycle, which are anabolic pathways, use the reverse reaction. Glycolysis, a catabolic pathway, uses the forward reaction. Aldolase is divided into two classes by mechanism.

<span class="mw-page-title-main">Ribose-5-phosphate isomerase</span>

Ribose-5-phosphate isomerase (Rpi) encoded by the RPIA gene is an enzyme that catalyzes the conversion between ribose-5-phosphate (R5P) and ribulose-5-phosphate (Ru5P). It is a member of a larger class of isomerases which catalyze the interconversion of chemical isomers. It plays a vital role in biochemical metabolism in both the pentose phosphate pathway and the Calvin cycle. The systematic name of this enzyme class is D-ribose-5-phosphate aldose-ketose-isomerase.

<span class="mw-page-title-main">Cystathionine beta-lyase</span> Enzyme

Cystathionine beta-lyase, also commonly referred to as CBL or β-cystathionase, is an enzyme that primarily catalyzes the following α,β-elimination reaction

<span class="mw-page-title-main">2-Dehydro-3-deoxy-phosphogluconate aldolase</span> Class of enzymes

The enzyme 2-dehydro-3-deoxy-phosphogluconate aldolase, commonly known as KDPG aldolase, catalyzes the chemical reaction

<span class="mw-page-title-main">Diaminopimelate decarboxylase</span> Enzyme decarboxylates diaminopimelate, forming L-lysine

The enzyme diaminopimelate decarboxylase (EC 4.1.1.20) catalyzes the cleavage of carbon-carbon bonds in meso-2,6-diaminoheptanedioate (diaminopimelate) to produce CO2 and L-lysine, the essential amino acid. It employs the cofactor pyridoxal phosphate, also known as PLP, which participates in numerous enzymatic transamination, decarboxylation and deamination reactions.

The enzyme phosphoketolase(EC 4.1.2.9) catalyzes the chemical reactions

<span class="mw-page-title-main">Aldolase C</span> Protein-coding gene in the species Homo sapiens

Aldolase C, fructose-bisphosphate, is an enzyme that, in humans, is encoded by the ALDOC gene on chromosome 17. This gene encodes a member of the class I fructose-bisphosphate aldolase gene family. Expressed specifically in the hippocampus and Purkinje cells of the brain, the encoded protein is a glycolytic enzyme that catalyzes the reversible aldol cleavage of fructose 1,6-bisphosphate and fructose-1-phosphate to dihydroxyacetone phosphate and either glyceraldehyde 3-phosphate or glyceraldehyde, respectively.[provided by RefSeq, Jul 2008]

<span class="mw-page-title-main">Transaldolase deficiency</span> Medical condition

Transaldolase deficiency is a disease characterised by abnormally low levels of the transaldolase enzyme. It is a metabolic enzyme involved in the pentose phosphate pathway. It is caused by mutation in the transaldolase gene (TALDO1). It was first described by Verhoeven et al. in 2001.

<span class="mw-page-title-main">Transaldolase 1</span> Protein-coding gene in the species Homo sapiens

Transaldolase 1 is a protein that in humans is encoded by the TALDO1 gene.

Sulfoglycolysis is a catabolic process in primary metabolism in which sulfoquinovose (6-deoxy-6-sulfonato-glucose) is metabolized to produce energy and carbon-building blocks. Sulfoglycolysis pathways occur in a wide variety of organisms, and enable key steps in the degradation of sulfoquinovosyl diacylglycerol (SQDG), a sulfolipid found in plants and cyanobacteria into sulfite and sulfate. Sulfoglycolysis converts sulfoquinovose (C6H12O8S) into various smaller metabolizable carbon fragments such as pyruvate and dihydroxyacetone phosphate that enter central metabolism. The free energy is used to form the high-energy molecules ATP (adenosine triphosphate) and NADH (reduced nicotinamide adenine dinucleotide). Unlike glycolysis, which allows metabolism of all carbons in glucose, sulfoglycolysis pathways convert only a fraction of the carbon content of sulfoquinovose into smaller metabolizable fragments; the remainder is excreted as C3-sulfonates 2,3-dihydroxypropanesulfonate (DHPS) or sulfolactate (SL); or C2-sulfonates isethionate or sulfoacetate.

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. Bibcode:2000FEBSL.475..205T. 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. Archived from the original on 2008-05-01. Retrieved 2008-12-19.