PDBsum entry 2ypi

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Triose phosphate isomerase PDB id
Protein chains
247 a.a. *
PGA ×2
Waters ×25
* Residue conservation analysis
PDB id:
Name: Triose phosphate isomerase
Title: Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5- angstroms resolution. Implications for catalysis
Structure: Triosephosphate isomerase. Chain: a, b. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.177    
Authors: E.Lolis,G.A.Petsko
Key ref:
E.Lolis and G.A.Petsko (1990). Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis. Biochemistry, 29, 6619-6625. PubMed id: 2204418 DOI: 10.1021/bi00480a010
12-Jan-90     Release date:   15-Jan-91    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00942  (TPIS_YEAST) -  Triosephosphate isomerase
248 a.a.
247 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!
  Cellular component     mitochondrion   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  


    Added reference    
DOI no: 10.1021/bi00480a010 Biochemistry 29:6619-6625 (1990)
PubMed id: 2204418  
Crystallographic analysis of the complex between triosephosphate isomerase and 2-phosphoglycolate at 2.5-A resolution: implications for catalysis.
E.Lolis, G.A.Petsko.
The binding of the transition-state analogue 2-phosphoglycolate to triosephosphate isomerase from yeast has been investigated crystallographically. An atomic model of the enzyme-inhibitor complex has been refined against data to 2.5-A resolution to a final R factor of 0.18. The interactions between the inhibitor and enzyme have been analyzed. The inhibitor forms hydrogen bonds to the side chains of His 95 and Glu 165. The latter hydrogen bond confirms that Glu 165 is protonated upon PGA binding. The structure of the complexed enzyme has been compared to that of the unbound form of the enzyme, and conformational changes have been observed: the side chain of Glu 165 moves over 2 A and a 10-residue flexible loop moves over 7 A to close over the active site. Spectroscopic results of phosphoglycolic acid binding to triosephosphate isomerase that have been amassed over the years are also explained in structural terms. The implications for catalysis are noted.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20877901 L.Cipolla, L.Gabrielli, D.Bini, L.Russo, and N.Shaikh (2010).
Kdo: a critical monosaccharide for bacteria viability.
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20694739 R.K.Wierenga, E.G.Kapetaniou, and R.Venkatesan (2010).
Triosephosphate isomerase: a highly evolved biocatalyst.
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19678695 C.A.Lewis, and R.Wolfenden (2009).
Orotic acid decarboxylation in water and nonpolar solvents: a potential role for desolvation in the action of OMP decarboxylase.
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19267450 L.J.Juszczak, and R.Z.Desamero (2009).
Extension of the tryptophan chi2,1 dihedral angle-W3 band frequency relationship to a full rotation: correlations and caveats.
  Biochemistry, 48, 2777-2787.  
19425580 M.K.Go, T.L.Amyes, and J.P.Richard (2009).
Hydron transfer catalyzed by triosephosphate isomerase. Products of the direct and phosphite-activated isomerization of [1-(13)C]-glycolaldehyde in D(2)O.
  Biochemistry, 48, 5769-5778.  
19089986 S.Donnini, A.Villa, G.Groenhof, A.E.Mark, R.K.Wierenga, and A.H.Juffer (2009).
Inclusion of ionization states of ligands in affinity calculations.
  Proteins, 76, 138-150.  
  19342791 S.Mukherjee, D.Dutta, B.Saha, and A.K.Das (2009).
Expression, purification, crystallization and preliminary X-ray diffraction studies of triosephosphate isomerase from methicillin-resistant Staphylococcus aureus (MRSA252).
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 398-401.  
19348462 Y.Wang, R.B.Berlow, and J.P.Loria (2009).
Role of loop-loop interactions in coordinating motions and enzymatic function in triosephosphate isomerase.
  Biochemistry, 48, 4548-4556.  
18547585 C.A.Smith, and T.Kortemme (2008).
Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction.
  J Mol Biol, 380, 742-756.  
18219118 M.Alahuhta, M.G.Casteleijn, P.Neubauer, and R.K.Wierenga (2008).
Structural studies show that the A178L mutation in the C-terminal hinge of the catalytic loop-6 of triosephosphate isomerase (TIM) induces a closed-like conformation in dimeric and monomeric TIM.
  Acta Crystallogr D Biol Crystallogr, 64, 178-188.
PDB codes: 2v0t 2v2c 2v2d 2v2h
18772387 S.M.Sullivan, and T.Holyoak (2008).
Enzymes with lid-gated active sites must operate by an induced fit mechanism instead of conformational selection.
  Proc Natl Acad Sci U S A, 105, 13829-13834.
PDB codes: 3dt2 3dt4 3dt7 3dtb
18376850 W.Y.Tsang, T.L.Amyes, and J.P.Richard (2008).
A substrate in pieces: allosteric activation of glycerol 3-phosphate dehydrogenase (NAD+) by phosphite dianion.
  Biochemistry, 47, 4575-4582.  
17336327 J.G.Kempf, J.Y.Jung, C.Ragain, N.S.Sampson, and J.P.Loria (2007).
Dynamic requirements for a functional protein hinge.
  J Mol Biol, 368, 131-149.  
17444661 T.L.Amyes, and J.P.Richard (2007).
Enzymatic catalysis of proton transfer at carbon: activation of triosephosphate isomerase by phosphite dianion.
  Biochemistry, 46, 5841-5854.  
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.  
15584080 S.Donnini, A.E.Mark, A.H.Juffer, and A.Villa (2005).
Incorporating the effect of ionic strength in free energy calculations using explicit ions.
  J Comput Chem, 26, 115-122.  
15324804 A.Tousignant, and J.N.Pelletier (2004).
Protein motions promote catalysis.
  Chem Biol, 11, 1037-1042.  
15218149 M.A.Dwyer, L.L.Looger, and H.W.Hellinga (2004).
Computational design of a biologically active enzyme.
  Science, 304, 1967-1971.  
15229879 P.K.Agarwal (2004).
Cis/trans isomerization in HIV-1 capsid protein catalyzed by cyclophilin A: insights from computational and theoretical studies.
  Proteins, 56, 449-463.  
12483674 G.Alagona, C.Ghio, and P.A.Kollman (2003).
The intramolecular mechanism for the second proton transfer in triosephosphate isomerase (TIM): a QM/FE approach.
  J Comput Chem, 24, 46-56.  
12509510 G.Jogl, S.Rozovsky, A.E.McDermott, and L.Tong (2003).
Optimal alignment for enzymatic proton transfer: structure of the Michaelis complex of triosephosphate isomerase at 1.2-A resolution.
  Proc Natl Acad Sci U S A, 100, 50-55.
PDB codes: 1ney 1nf0
12522213 I.Kursula, and R.K.Wierenga (2003).
Crystal structure of triosephosphate isomerase complexed with 2-phosphoglycolate at 0.83-A resolution.
  J Biol Chem, 278, 9544-9551.
PDB code: 1n55
14563846 S.Parthasarathy, K.Eaazhisai, H.Balaram, P.Balaram, and M.R.Murthy (2003).
Structure of Plasmodium falciparum triose-phosphate isomerase-2-phosphoglycerate complex at 1.1-A resolution.
  J Biol Chem, 278, 52461-52470.
PDB code: 1o5x
12805358 T.C.Meredith, and R.W.Woodard (2003).
Escherichia coli YrbH is a D-arabinose 5-phosphate isomerase.
  J Biol Chem, 278, 32771-32777.  
11741996 Z.Hou, W.Wang, H.J.Fromm, and R.B.Honzatko (2002).
IMP Alone Organizes the Active Site of Adenylosuccinate Synthetase from Escherichia coli.
  J Biol Chem, 277, 5970-5976.
PDB codes: 1kjx 1kkb 1kkf
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.  
11589711 I.Kursula, S.Partanen, A.M.Lambeir, D.M.Antonov, K.Augustyns, and R.K.Wierenga (2001).
Structural determinants for ligand binding and catalysis of triosephosphate isomerase.
  Eur J Biochem, 268, 5189-5196.
PDB code: 1if2
11568181 M.L.Ferri-Fioni, E.Schmitt, J.Soutourina, P.Plateau, Y.Mechulam, and S.Blanquet (2001).
Structure of crystalline D-Tyr-tRNA(Tyr) deacylase. A representative of a new class of tRNA-dependent hydrolases.
  J Biol Chem, 276, 47285-47290.
PDB code: 1jke
10692347 A.Jutila, K.Zhu, S.A.Patkar, J.Vind, A.Svendsen, and P.K.Kinnunen (2000).
Detergent-induced conformational changes of Humicola lanuginosa lipase studied by fluorescence spectroscopy.
  Biophys J, 78, 1634-1642.  
9891798 J.M.Shively, G.van Keulen, and W.G.Meijer (1998).
Something from almost nothing: carbon dioxide fixation in chemoautotrophs.
  Annu Rev Microbiol, 52, 191-230.  
  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.  
9449311 P.Derreumaux, and T.Schlick (1998).
The loop opening/closing motion of the enzyme triosephosphate isomerase.
  Biophys J, 74, 72-81.  
10089540 R.Gilboa, A.J.Bauer, and G.Shoham (1998).
Crystallization and preliminary crystallographic analysis of glyceraldehyde 3-phosphate dehydrogenase from Sacchromyces cerevisiae (baker's yeast).
  Acta Crystallogr D Biol Crystallogr, 54, 1467-1470.  
  10082378 S.Ishii, H.Hayashi, A.Okamoto, and H.Kagamiyama (1998).
Aromatic L-amino acid decarboxylase: conformational change in the flexible region around Arg334 is required during the transaldimination process.
  Protein Sci, 7, 1802-1810.  
  9514261 Y.Cao, R.A.Musah, S.K.Wilcox, D.B.Goodin, and D.E.McRee (1998).
Protein conformer selection by ligand binding observed with crystallography.
  Protein Sci, 7, 72-78.
PDB code: 1ccj
9020588 P.Pan, E.Woehl, and M.F.Dunn (1997).
Protein architecture, dynamics and allostery in tryptophan synthase channeling.
  Trends Biochem Sci, 22, 22-27.  
8807818 A.Gómez-Puyou, E.Saavedra-Lira, I.Becker, R.A.Zubillaga, A.Rojo-Domínguez, and R.Pérez-Montfort (1995).
Using evolutionary changes to achieve species-specific inhibition of enzyme action--studies with triosephosphate isomerase.
  Chem Biol, 2, 847-855.  
7540485 J.Zhang, F.Zhang, D.Ebert, M.H.Cobb, and E.J.Goldsmith (1995).
Activity of the MAP kinase ERK2 is controlled by a flexible surface loop.
  Structure, 3, 299-307.  
  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
8591044 T.V.Borchert, K.V.Kishan, J.P.Zeelen, W.Schliebs, N.Thanki, R.Abagyan, R.Jaenicke, and R.K.Wierenga (1995).
Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8.
  Structure, 3, 669-679.
PDB codes: 1mss 1tti 1ttj
  7757001 N.V.Grishin, and M.A.Phillips (1994).
The subunit interfaces of oligomeric enzymes are conserved to a similar extent to the overall protein sequences.
  Protein Sci, 3, 2455-2458.  
7876898 P.L.Chau, and P.M.Dean (1994).
Electrostatic complementarity between proteins and ligands. 1. Charge disposition, dielectric and interface effects.
  J Comput Aided Mol Des, 8, 513-525.  
7656010 R.C.Wade, B.A.Luty, E.Demchuk, J.D.Madura, M.E.Davis, J.M.Briggs, and J.A.McCammon (1994).
Simulation of enzyme-substrate encounter with gated active sites.
  Nat Struct Biol, 1, 65-69.  
  8061610 S.C.Mande, V.Mainfroid, K.H.Kalk, K.Goraj, J.A.Martial, and W.G.Hol (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.
PDB code: 1hti
8356028 M.E.Noble, J.P.Zeelen, and R.K.Wierenga (1993).
Structures of the "open" and "closed" state of trypanosomal triosephosphate isomerase, as observed in a new crystal form: implications for the reaction mechanism.
  Proteins, 16, 311-326.
PDB codes: 1tpd 1trd 2v5l
8433995 M.Wilmanns, and D.Eisenberg (1993).
Three-dimensional profiles from residue-pair preferences: identification of sequences with beta/alpha-barrel fold.
  Proc Natl Acad Sci U S A, 90, 1379-1383.  
8431552 R.C.Wade, M.E.Davis, B.A.Luty, J.D.Madura, and J.A.McCammon (1993).
Gating of the active site of triose phosphate isomerase: Brownian dynamics simulations of flexible peptide loops in the enzyme.
  Biophys J, 64, 9.  
8244340 S.Hollán, H.Fujii, A.Hirono, K.Hirono, H.Karro, S.Miwa, V.Harsányi, E.Gyódi, and M.Inselt-Kovács (1993).
Hereditary triosephosphate isomerase (TPI) deficiency: two severely affected brothers one with and one without neurological symptoms.
  Hum Genet, 92, 486-490.  
  1304395 A.E.Howard, and P.A.Kollman (1992).
Molecular dynamics studies of a DNA-binding protein: 1. A comparison of the trp repressor and trp aporepressor aqueous simulations.
  Protein Sci, 1, 1173-1184.  
  1304889 C.L.Verlinde, C.J.Witmans, T.Pijning, K.H.Kalk, W.G.Hol, M.Callens, and F.R.Opperdoes (1992).
Structure of the complex between trypanosomal triosephosphate isomerase and N-hydroxy-4-phosphono-butanamide: binding at the active site despite an "open" flexible loop conformation.
  Protein Sci, 1, 1578-1584.
PDB code: 1tsi
1528078 M.D.Walkinshaw (1992).
Protein targets for structure-based drug design.
  Med Res Rev, 12, 317-372.  
1639191 R.K.Wierenga, T.V.Borchert, and M.E.Noble (1992).
Crystallographic binding studies with triosephosphate isomerases: conformational changes induced by substrate and substrate-analogues.
  FEBS Lett, 307, 34-39.  
2065677 K.D.Schnackerz, and R.W.Gracy (1991).
Probing the catalytic sites of triosephosphate isomerase by 31P-NMR with reversibly and irreversibly binding substrate analogues.
  Eur J Biochem, 199, 231-238.  
2062828 M.E.Noble, R.K.Wierenga, A.M.Lambeir, F.R.Opperdoes, A.M.Thunnissen, K.H.Kalk, H.Groendijk, and W.G.Hol (1991).
The adaptability of the active site of trypanosomal triosephosphate isomerase as observed in the crystal structures of three different complexes.
  Proteins, 10, 50-69.
PDB codes: 1iig 1iih 6tim
2062827 R.K.Wierenga, M.E.Noble, J.P.Postma, H.Groendijk, K.H.Kalk, W.G.Hol, and F.R.Opperdoes (1991).
The crystal structure of the "open" and the "closed" conformation of the flexible loop of trypanosomal triosephosphate isomerase.
  Proteins, 10, 33-49.
PDB codes: 2tim 3tim
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