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PDBsum entry 1m7p

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
1m7p
Jmol
Contents
Protein chains
246 a.a. *
Ligands
G3H ×2
Waters ×135
* Residue conservation analysis
PDB id:
1m7p
Name: Isomerase
Title: Plasmodium falciparum triosephosphate isomerase (pftim) compled to substrate analog glycerol-3-phosphate (g3p).
Structure: Triosephosphate isomerase. Chain: a, b. Synonym: tim. Triose-phosphate isomerase. Triose phosphate isomerase. Engineered: yes
Source: Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Gene: tpi. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.179     R-free:   0.216
Authors: S.Parthasarathy,H.Balaram,P.Balaram,M.R.N.Murthy
Key ref:
S.Parthasarathy et al. (2002). Structures of Plasmodium falciparum triosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state. Acta Crystallogr D Biol Crystallogr, 58, 1992-2000. PubMed id: 12454456 DOI: 10.1107/S0907444902015433
Date:
22-Jul-02     Release date:   29-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q07412  (TPIS_PLAFA) -  Triosephosphate isomerase
Seq:
Struc:
248 a.a.
246 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.5.3.1.1  - Triose-phosphate isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate = glycerone phosphate
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = G3H)
corresponds exactly
= 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: 10.1107/S0907444902015433 Acta Crystallogr D Biol Crystallogr 58:1992-2000 (2002)
PubMed id: 12454456  
 
 
Structures of Plasmodium falciparum triosephosphate isomerase complexed to substrate analogues: observation of the catalytic loop in the open conformation in the ligand-bound state.
S.Parthasarathy, H.Balaram, P.Balaram, M.R.Murthy.
 
  ABSTRACT  
 
The glycolytic enzymes of Plasmodium falciparum (Pf) are attractive drug targets as the parasites lack a functional tricarboxylic cycle and hence depend heavily on glycolysis for their energy requirements. Structural comparisons between Pf triosephosphate isomerase (PfTIM) and its human homologue have highlighted the important differences between the host and parasite enzymes [Velanker et al. (1997), Structure, 5, 751-761]. Structures of various PfTIM-ligand complexes have been determined in order to gain further insight into the mode of inhibitor binding to the parasite enzyme. Structures of two PfTIM-substrate analogue complexes, those of 3-phosphoglycerate (3PG) and glycerol-3-phosphate (G3P), have been determined and refined at 2.4 A resolution. Both complexes crystallized in the monoclinic space group P2(1), with a molecular dimer in the asymmetric unit. The novel aspect of these structures is the adoption of the 'loop-open' conformation, with the catalytic loop (loop 6, residues 166-176) positioned away from the active site; this loop is known to move by about 7 A towards the active site upon inhibitor binding in other TIMs. The loop-open form in the PfTIM complexes appears to be a consequence of the S96F mutation, which is specific to the enzymes from malarial parasites. Structural comparison with the corresponding complexes of Trypanosoma brucei TIM (TrypTIM) shows that extensive steric clashes may be anticipated between Phe96 and Ile172 in the 'closed' conformation of the catalytic loop, preventing loop closure in PfTIM. Ser73 in PfTIM (Ala in all other known TIMs) appears to provide an anchoring water-mediated hydrogen bond to the ligand, compensating for the loss of a stabilizing hydrogen bond from Gly171 NH in the closed-loop liganded TIM structures.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Chemical structures of the substrate analogues 3-phosphoglycerate (3PG) and glycerol-3-phosphate (G3P) (a). mF[o] - DF[c] omit maps for the ligand 3PG (b) and G3P (c) at the end of the refinement. Maps are contoured at 2.2 .
Figure 6.
Figure 6 Schematic representation showing the anticipated steric clash between Phe96 and Ile172 of PfTIM in a closed-loop conformation. The figure was generated superposing the PfTIM-3PG structure and the closed-loop TrypTIM structure (PDB code [184]1iig ). van der Waals surfaces for Phe96, Ile (172 in Pf and 174 in TrypTIMs) and 3PG are shown.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2002, 58, 1992-2000) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
17957775 C.H.Chu, Y.J.Lai, H.Huang, and Y.J.Sun (2008).
Kinetic and structural properties of triosephosphate isomerase from Helicobacter pylori.
  Proteins, 71, 396-406.
PDB code: 2jgq
17646926 K.H.Kim (2007).
Outliers in SAR and QSAR: 2. Is a flexible binding site a possible source of outliers?
  J Comput Aided Mol Des, 21, 421-435.  
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
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.