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Isomerase(intramolecular oxidoreductase) PDB id
Protein chain
248 a.a. *
* Residue conservation analysis
PDB id:
Name: Isomerase(intramolecular oxidoreductase)
Title: Crystal structure of recombinant human triosephosphate isomerase at 2.8 angstroms resolution. Triosephosphate isomerase related human genetic disorders and comparison with the trypanosomal enzyme
Structure: Triosephosphate isomerase. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
2.80Å     R-factor:   0.167    
Authors: S.C.Mande,W.G.J.Hol
Key ref:
S.C.Mande et al. (1994). Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme. Protein Sci, 3, 810-821. PubMed id: 8061610 DOI: 10.1002/pro.5560030510
12-Oct-94     Release date:   26-Jan-95    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P60174  (TPIS_HUMAN) -  Triosephosphate isomerase
286 a.a.
248 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Triose-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = PGA)
matches with 72.00% similarity
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     2 terms  


    Added reference    
DOI no: 10.1002/pro.5560030510 Protein Sci 3:810-821 (1994)
PubMed id: 8061610  
Crystal structure of recombinant human triosephosphate isomerase at 2.8 A resolution. Triosephosphate isomerase-related human genetic disorders and comparison with the trypanosomal enzyme.
S.C.Mande, V.Mainfroid, K.H.Kalk, K.Goraj, J.A.Martial, W.G.Hol.
The crystal structure of recombinant human triosephosphate isomerase (hTIM) has been determined complexed with the transition-state analogue 2-phosphoglycolate at a resolution of 2.8 A. After refinement, the R-factor is 16.7% with good geometry. The asymmetric unit contains 1 complete dimer of 53,000 Da, with only 1 of the subunits binding the inhibitor. The so-called flexible loop, comprising residues 168-174, is in its "closed" conformation in the subunit that binds the inhibitor, and in the "open" conformation in the other subunit. The tips of the loop in these 2 conformations differ up to 7 A in position. The RMS difference between hTIM and the enzyme of Trypanosoma brucei, the causative agent of sleeping sickness, is 1.12 A for 487 C alpha positions with 53% sequence identity. Significant sequence differences between the human and parasite enzymes occur at about 13 A from the phosphate binding site. The chicken and human enzymes have an RMS difference of 0.69 A for 484 equivalent residues and about 90% sequence identity. Complementary mutations ensure a great similarity in the packing of side chains in the core of the beta-barrels of these 2 enzymes. Three point mutations in hTIM have been correlated with severe genetic disorders ranging from hemolytic disorder to neuromuscular impairment. Knowledge of the structure of the human enzyme provides insight into the probable effect of 2 of these mutations, Glu 104 to Asp and Phe 240 to Ile, on the enzyme. The third mutation reported to be responsible for a genetic disorder, Gly 122 to Arg, is however difficult to explain. This residue is far away from both catalytic centers in the dimer, as well as from the dimer interface, and seems unlikely to affect stability or activity. Inspection of the 3-dimensional structure of trypanosomal triosephosphate isomerase, which has a methionine at position 122, only increased the mystery of the effects of the Gly to Arg mutation in the human enzyme.
  Selected figure(s)  
Figure 5.
Fig. 5. Interactionsof -PC withhTIM. The 3,,,-helix,compisingresidues533- 537, points directly n the phosphate moiety. Also hown is the unusual phosphate-carbonyl (Gly 510) interac- tion. This figure was produced using MOLSCRIPT.
Figure 8.
Fig. 8.Mutation of phenylalanine to at position 240 resulting in genetic disorder in hTIM (Chang et 993). The and the 2-PG molecule are shown in ball-and-stick representations. The orientation is cho- sensuch thatthe 310-helixisseen point- ing toward the phosphate. The adjoining &strand is shown terminating in the cat- alytic Lys313.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1994, 3, 810-821) copyright 1994.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18458110 J.L.Seigle, A.M.Celotto, and M.J.Palladino (2008).
Degradation of functional triose phosphate isomerase protein underlies sugarkill pathology.
  Genetics, 179, 855-862.  
17337581 M.Rhimi, M.Juy, N.Aghajari, R.Haser, and S.Bejar (2007).
Probing the essential catalytic residues and substrate affinity in the thermoactive Bacillus stearothermophilus US100 L-arabinose isomerase by site-directed mutagenesis.
  J Bacteriol, 189, 3556-3563.  
17566975 R.Pedreschi, E.Vanstreels, S.Carpentier, M.Hertog, J.Lammertyn, J.Robben, J.P.Noben, R.Swennen, J.Vanderleyden, and B.M.Nicolaï (2007).
Proteomic analysis of core breakdown disorder in Conference pears (Pyrus communis L.).
  Proteomics, 7, 2083-2099.  
16980388 A.M.Celotto, A.C.Frank, J.L.Seigle, and M.J.Palladino (2006).
Drosophila model of human inherited triosephosphate isomerase deficiency glycolytic enzymopathy.
  Genetics, 174, 1237-1246.  
16323206 F.A.Konuklar, V.Aviyente, and T.Halilo─člu (2006).
Coupling of structural fluctuations to deamidation reaction in triosephosphate isomerase by Gaussian network model.
  Proteins, 62, 715-727.  
16503298 H.Adachi, A.Niino, T.Kinoshita, M.Warizaya, R.Maruki, K.Takano, H.Matsumura, T.Inoue, S.Murakami, Y.Mori, and T.Sasaki (2006).
Solution-stirring method improves crystal quality of human triosephosphate isomerase.
  J Biosci Bioeng, 101, 83-86.  
  16511037 T.Kinoshita, R.Maruki, M.Warizaya, H.Nakajima, and S.Nishimura (2005).
Structure of a high-resolution crystal form of human triosephosphate isomerase: improvement of crystals using the gel-tube method.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 346-349.
PDB code: 1wyi
14648757 S.L.Lowe, C.Adrian, I.V.Ouporov, V.F.Waingeh, and K.A.Thomasson (2003).
Brownian dynamics simulations of glycolytic enzyme subsets with F-actin.
  Biopolymers, 70, 456-470.  
12554940 T.Kinoshita, N.Nishio, I.Nakanishi, A.Sato, and T.Fujii (2003).
Structure of bovine adenosine deaminase complexed with 6-hydroxy-1,6-dihydropurine riboside.
  Acta Crystallogr D Biol Crystallogr, 59, 299-303.
PDB code: 1krm
14674757 V.H.Moreau, A.W.Rietveld, and S.T.Ferreira (2003).
Persistent conformational heterogeneity of triosephosphate isomerase: separation and characterization of conformational isomers in solution.
  Biochemistry, 42, 14831-14837.  
12112681 H.Reyes-Vivas, E.Martínez-Martínez, G.Mendoza-Hernández, G.López-Velázquez, R.Pérez-Montfort, M.Tuena de Gómez-Puyou, and A.Gómez-Puyou (2002).
Susceptibility to proteolysis of triosephosphate isomerase from two pathogenic parasites: characterization of an enzyme with an intact and a nicked monomer.
  Proteins, 48, 580-590.  
11562943 F.Joubert, A.W.Neitz, and A.I.Louw (2001).
Structure-based inhibitor screening: a family of sulfonated dye inhibitors for malaria parasite triosephosphate isomerase.
  Proteins, 45, 136-143.  
11258928 H.Reyes-Vivas, G.Hernández-Alcantara, G.López-Velazquez, N.Cabrera, R.Pérez-Montfort, Gómez-Puyou, and A.Gómez-Puyou (2001).
Factors that control the reactivity of the interface cysteine of triosephosphate isomerase from Trypanosoma brucei and Trypanosoma cruzi.
  Biochemistry, 40, 3134-3140.  
11296285 N.E.Robinson, and A.B.Robinson (2001).
Prediction of protein deamidation rates from primary and three-dimensional structure.
  Proc Natl Acad Sci U S A, 98, 4367-4372.  
10655478 F.Orosz, G.Wágner, K.Liliom, J.Kovács, K.Baróti, M.Horányi, T.Farkas, S.Hollán, and J.Ovádi (2000).
Enhanced association of mutant triosephosphate isomerase to red cell membranes and to brain microtubules.
  Proc Natl Acad Sci U S A, 97, 1026-1031.  
11053862 R.Aparicio, S.T.Ferreira, N.R.Leite, and I.Polikarpov (2000).
Preliminary X-ray diffraction studies of rabbit muscle triose phosphate isomerase (TIM).
  Acta Crystallogr D Biol Crystallogr, 56, 1492-1494.
PDB code: 1r43
10591103 D.Maes, J.P.Zeelen, N.Thanki, N.Beaucamp, M.Alvarez, M.H.Thi, J.Backmann, J.A.Martial, L.Wyns, R.Jaenicke, and R.K.Wierenga (1999).
The crystal structure of triosephosphate isomerase (TIM) from Thermotoga maritima: a comparative thermostability structural analysis of ten different TIM structures.
  Proteins, 37, 441-453.
PDB code: 1b9b
10535937 E.M.Khalil, J.De Angelis, M.Ishii, and P.A.Cole (1999).
Mechanism-based inhibition of the melatonin rhythm enzyme: pharmacologic exploitation of active site functional plasticity.
  Proc Natl Acad Sci U S A, 96, 12418-12423.  
10194326 R.Pérez-Montfort, G.Garza-Ramos, G.H.Alcántara, H.Reyes-Vivas, X.G.Gao, E.Maldonado, Gómez-Puyou, and A.Gómez-Puyou (1999).
Derivatization of the interface cysteine of triosephosphate isomerase from Trypanosoma brucei and Trypanosoma cruzi as probe of the interrelationship between the catalytic sites and the dimer interface.
  Biochemistry, 38, 4114-4120.  
10049939 R.Pieper, R.E.Christian, M.I.Gonzales, M.I.Nishimura, G.Gupta, R.E.Settlage, J.Shabanowitz, S.A.Rosenberg, D.F.Hunt, and S.L.Topalian (1999).
Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells.
  J Exp Med, 189, 757-766.  
10468562 X.G.Gao, E.Maldonado, R.Pérez-Montfort, G.Garza-Ramos, Gómez-Puyou, A.Gómez-Puyou, and A.Rodríguez-Romero (1999).
Crystal structure of triosephosphate isomerase from Trypanosoma cruzi in hexane.
  Proc Natl Acad Sci U S A, 96, 10062-10067.
PDB code: 1ci1
10089525 G.S.Bell, R.J.Russell, M.Kohlhoff, R.Hensel, M.J.Danson, D.W.Hough, and G.L.Taylor (1998).
Preliminary crystallographic studies of triosephosphate isomerase (TIM) from the hyperthermophilic Archaeon Pyrococcus woesei.
  Acta Crystallogr D Biol Crystallogr, 54, 1419-1421.  
  9684881 J.Sun, and N.S.Sampson (1998).
Determination of the amino acid requirements for a protein hinge in triosephosphate isomerase.
  Protein Sci, 7, 1495-1505.  
9723162 R.W.Gracy, J.M.Talent, and A.I.Zvaigzne (1998).
Molecular wear and tear leads to terminal marking and the unstable isoforms of aging.
  J Exp Zool, 282, 18-27.  
9249046 A.Landa, A.Rojo-Domínguez, L.Jiménez, and D.A.Fernández-Velasco (1997).
Sequencing, expression and properties of triosephosphate isomerase from Entamoeba histolytica.
  Eur J Biochem, 247, 348-355.  
8898895 G.Garza-Ramos, R.Pérez-Montfort, A.Rojo-Domínguez, Gómez-Puyou, and A.Gómez-Puyou (1996).
Species-specific inhibition of homologous enzymes by modification of nonconserved amino acids residues. The cysteine residues of triosephosphate isomerase.
  Eur J Biochem, 241, 114-120.  
8961958 M.A.Sepúlveda-Becerra, S.T.Ferreira, R.J.Strasser, W.Garzón-Rodríguez, C.Beltrán, A.Gómez-Puyou, and A.Darszon (1996).
Refolding of triosephosphate isomerase in low-water media investigated by fluorescence resonance energy transfer.
  Biochemistry, 35, 15915-15922.  
  8571957 M.Watanabe, B.C.Zingg, and H.W.Mohrenweiser (1996).
Molecular analysis of a series of alleles in humans with reduced activity at the triosephosphate isomerase locus.
  Am J Hum Genet, 58, 308-316.  
8672446 V.Mainfroid, S.C.Mande, W.G.Hol, J.A.Martial, and K.Goraj (1996).
Stabilization of human triosephosphate isomerase by improvement of the stability of individual alpha-helices in dimeric as well as monomeric forms of the protein.
  Biochemistry, 35, 4110-4117.  
  8580851 L.F.Delboni, S.C.Mande, F.Rentier-Delrue, V.Mainfroid, S.Turley, F.M.Vellieux, J.A.Martial, and W.G.Hol (1995).
Crystal structure of recombinant triosephosphate isomerase from Bacillus stearothermophilus. An analysis of potential thermostability factors in six isomerases with known three-dimensional structures points to the importance of hydrophobic interactions.
  Protein Sci, 4, 2594-2604.
PDB code: 1btm
  7849584 C.L.Verlinde, E.A.Merritt, F.Van den Akker, H.Kim, I.Feil, L.F.Delboni, S.C.Mande, S.Sarfaty, P.H.Petra, and W.G.Hol (1994).
Protein crystallography and infectious diseases.
  Protein Sci, 3, 1670-1686.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.