PDBsum entry 1woa

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Isomerase PDB id
Protein chains
246 a.a. *
G2H ×4
Waters ×142
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Structure of the loop6 hinge mutant of plasmodium falciparum triosephosphate isomerase, w168f, complexed with glycerol-2-phosphate
Structure: Triosephosphate isomerase. Chain: a, b, c, d. Synonym: tim. Engineered: yes. Mutation: yes
Source: Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.80Å     R-factor:   0.219     R-free:   0.252
Authors: K.Eaazhisai,H.Balaram,P.Balaram,M.R.N.Murthy
Key ref:
K.Eaazhisai et al. (2004). Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge mutant of Plasmodium falciparum triosephosphate isomerase: observation of an intermediate position of loop6. J Mol Biol, 343, 671-684. PubMed id: 15465054 DOI: 10.1016/j.jmb.2004.08.060
12-Aug-04     Release date:   26-Oct-04    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q07412  (TPIS_PLAFA) -  Triosephosphate isomerase
248 a.a.
246 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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 = G2H)
matches with 66.00% 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   4 terms 
  Biochemical function     catalytic activity     4 terms  


    Added reference    
DOI no: 10.1016/j.jmb.2004.08.060 J Mol Biol 343:671-684 (2004)
PubMed id: 15465054  
Structures of unliganded and inhibitor complexes of W168F, a Loop6 hinge mutant of Plasmodium falciparum triosephosphate isomerase: observation of an intermediate position of loop6.
K.Eaazhisai, H.Balaram, P.Balaram, M.R.Murthy.
The enzymatic reaction of triosephosphate isomerase (TIM) is controlled by the movement of a loop (loop6, residues 166-176). Crystal structures of TIMs from a variety of sources have revealed that the loop6, which is in an open conformation in the unliganded enzyme, adopts a closed conformation in inhibitor complexes. In contrast, structures with loop open conformation are obtained in most of the complexes of TIM from the malarial parasite Plasmodium falciparum (PfTIM). W168 is a conserved N-terminal hinge residue, involved in different sets of interactions in the "open" and "closed" forms of loop6. The role of W168 in determining the loop conformation was examined by structural studies on the mutant W168F and its complexes with ligands. The three-dimensional structures of unliganded mutant (1.8 A) and complexes with sulfate (2.8 A) and glycerol-2-phosphate (G2P) (2.8 A) have been determined. Loop6 was found disordered in these structures, reflecting the importance of W168 in stabilizing either the open or the closed states. Critical sequence differences between the Plasmodium enzyme and other TIMs may influence the equilibrium between the closed and open forms. Examination of the environment of the loop6 shows that its propensity for the open or the closed forms is influenced not only by Phe96 as suggested earlier, but also by Asn233, which occurs in the vicinity of the active site. This residue is Gly in the other TIM sequences and probably plays a crucial role in the mode of ligand binding, which in turn affects the loop opening/closing process in PfTIM.
  Selected figure(s)  
Figure 1.
Figure 1. (a) Ribbon representation of the structure of PfTIM monomer. Trp11 (blue) and Trp168 (green) are shown in sticks. (b) and (c) Hydrogen bonding interactions of the N-terminal hinge residues, Pro166, Leu167 and Trp168 in the open and closed forms of loop6, respectively. The Figures were generated using MOLSCRIPT39 and rendered using Raster3D.40 (d) Chemical structures of the substrates and various ligands of TIM; dihydroxyacetone phosphate (DHAP), glyceraldehyde-3-phosphate (GAP), 2-phosphoglycolate (PGA), 2-phosphoglycerate (2PG), glycerol-3-phosphate (G-3P) and glycerol-2-phosphate (G-2P).
Figure 3.
Figure 3. Stereo view of the ligand binding site in the structures of W168F mutant of PfTIM complexed with sulfate and G2P. (a) Fit of the sulfate ion to the electron density in a F[obs] -F[calc] omit map contoured at 2.5s. (b) Superposition of the active sites of sulfate complexes of TrypTIM (green), C. elegans TIM (indigo) and W168F mutant of PfTIM (colored by atom) showing the differences in the protein-ligand interactions. (c) G2P at the active site of the B-subunit of W168F-G2P complex is shown with density from the F[obs] -F[calc] omit map contoured at 2.5s. (d) Hydrogen bonding interactions (dotted lines) of G2P with the polypeptide.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 671-684) copyright 2004.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21396445 J.Moraes, R.Arreola, N.Cabrera, L.Saramago, D.Freitas, A.Masuda, I.da Silva Vaz, M.Tuena de Gomez-Puyou, R.Perez-Montfort, A.Gomez-Puyou, and C.Logullo (2011).
Structural and biochemical characterization of a recombinant triosephosphate isomerase from Rhipicephalus (Boophilus) microplus.
  Insect Biochem Mol Biol, 41, 400-409.
PDB code: 3th6
19296440 B.Taneja, J.Yadav, T.K.Chakraborty, and S.K.Brahmachari (2009).
An Indian effort towards affordable drugs: "generic to designer drugs".
  Biotechnol J, 4, 348-360.  
19261703 S.S.Thakur, P.D.Deepalakshmi, P.Gayathri, M.Banerjee, M.R.Murthy, and P.Balaram (2009).
Detection of the protein dimers, multiple monomeric states and hydrated forms of Plasmodium falciparum triosephosphate isomerase in the gas phase.
  Protein Eng Des Sel, 22, 289-304.  
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
17242514 P.Gayathri, M.Banerjee, A.Vijayalakshmi, S.Azeez, H.Balaram, P.Balaram, and M.R.Murthy (2007).
Structure of triosephosphate isomerase (TIM) from Methanocaldococcus jannaschii.
  Acta Crystallogr D Biol Crystallogr, 63, 206-220.
PDB code: 2h6r
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.  
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.