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PDBsum entry 1ydv

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protein Protein-protein interface(s) links
Isomerase PDB id
1ydv
Jmol
Contents
Protein chains
246 a.a. *
Waters ×171
* Residue conservation analysis
PDB id:
1ydv
Name: Isomerase
Title: Triosephosphate isomerase (tim)
Structure: Triosephosphate isomerase. Chain: a, b. Synonym: tim. Engineered: yes
Source: Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
2.20Å     R-factor:   0.198     R-free:   0.255
Authors: S.S.Velankar,M.R.N.Murthy
Key ref:
S.S.Velanker et al. (1997). Triosephosphate isomerase from Plasmodium falciparum: the crystal structure provides insights into antimalarial drug design. Structure, 5, 751-761. PubMed id: 9261072 DOI: 10.1016/S0969-2126(97)00230-X
Date:
24-Apr-97     Release date:   15-Oct-97    
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
= 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/S0969-2126(97)00230-X Structure 5:751-761 (1997)
PubMed id: 9261072  
 
 
Triosephosphate isomerase from Plasmodium falciparum: the crystal structure provides insights into antimalarial drug design.
S.S.Velanker, S.S.Ray, R.S.Gokhale, S.Suma, H.Balaram, P.Balaram, M.R.Murthy.
 
  ABSTRACT  
 
BACKGROUND: Malaria caused by the parasite Plasmodium falciparum is a major public health concern. The parasite lacks a functional tricarboxylic acid cycle, making glycolysis its sole energy source. Although parasite enzymes have been considered as potential antimalarial drug targets, little is known about their structural biology. Here we report the crystal structure of triosephosphate isomerase (TIM) from P. falciparum at 2.2 A resolution. RESULTS: The crystal structure of P. falciparum TIM (PfTIM), expressed in Escherichia coli, was determined by the molecular replacement method using the structure of trypanosomal TIM as the starting model. Comparison of the PfTIM structure with other TIM structures, particularly human TIM, revealed several differences. In most TIMs the residue at position 183 is a glutamate but in PfTIM it is a leucine. This leucine residue is completely exposed and together with the surrounding positively charged patch, may be responsible for binding TIM to the erythrocyte membrane. Another interesting feature is the occurrence of a cysteine residue at the dimer interface of PfTIM (Cys13), in contrast to human TIM where this residue is a methionine. Finally, residue 96 of human TIM (Ser96), which occurs near the active site, has been replaced by phenylalanine in PfTIM. CONCLUSIONS: Although the human and Plasmodium enzymes share 42% amino acid sequence identity, several key differences suggest that PfTIM may turn out to be a potential drug target. We have identified a region which may be responsible for binding PfTIM to cytoskeletal elements or the band 3 protein of erythrocytes; attachment to the erythrocyte membrane may subsequently lead to the extracellular exposure of parts of the protein. This feature may be important in view of a recent report that patients suffering from P. falciparum malaria mount an antibody response to TIM leading to prolonged hemolysis. A second approach to drug design may be provided by the mutation of the largely conserved residue (Ser96) to phenylalanine in PfTIM. This difference may be of importance in designing specific active-site inhibitors against the enzyme. Finally, specific inhibition of PfTIM subunit assembly might be possible by targeting Cys13 at the dimer interface. The crystal structure of PfTIM provides a framework for new therapeutic leads.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Comparison of the charge distribution on the surface of (a) PfTIM and (b) human TIM around residue Leu183. The residues Leu183 and Glu165 (in PfTIM) and Glu183 and Glu165 (in human TIM) are labeled. Red and blue represent negatively and positively charged regions, respectively, on the protein surface. (The figure was made using the program GRASP [52].)
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 751-761) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20602244 E.Tolonen, B.Bueno, S.Kulshreshta, P.Cieplak, M.Argáez, L.Velázquez, and B.Stec (2011).
Allosteric transition and binding of small molecule effectors causes curvature change in central β-sheets of selected enzymes.
  J Mol Model, 17, 899-911.  
  21447068 M.Samanta, M.Banerjee, M.R.Murthy, H.Balaram, and P.Balaram (2011).
Probing the role of the fully conserved Cys126 in triosephosphate isomerase by site-specific mutagenesis - distal effects on dimer stability.
  FEBS J, 278, 1932-1943.
PDB codes: 3pvf 3pwa 3py2
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.  
18500983 Y.Joubert, and F.Joubert (2008).
A structural annotation resource for the selection of putative target proteins in the malaria parasite.
  Malar J, 7, 90.  
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.  
17875391 P.Gayathri, H.Balaram, and M.R.Murthy (2007).
Structural biology of plasmodial proteins.
  Curr Opin Struct Biol, 17, 744-754.  
17295358 S.K.Gupta, B.S.Sisodia, S.Sinha, K.Hajela, S.Naik, A.K.Shasany, and A.Dube (2007).
Proteomic approach for identification and characterization of novel immunostimulatory proteins from soluble antigens of Leishmania donovani promastigotes.
  Proteomics, 7, 816-823.  
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
15146481 G.López-Velázquez, D.Molina-Ortiz, N.Cabrera, G.Hernández-Alcántara, J.Peon-Peralta, L.Yépez-Mulia, R.Pérez-Montfort, and H.Reyes-Vivas (2004).
An unusual triosephosphate isomerase from the early divergent eukaryote Giardia lamblia.
  Proteins, 55, 824-834.  
15606772 I.Pal-Bhowmick, K.Sadagopan, H.K.Vora, A.Sehgal, S.Sharma, and G.K.Jarori (2004).
Cloning, over-expression, purification and characterization of Plasmodium falciparum enolase.
  Eur J Biochem, 271, 4845-4854.  
12581214 P.Pattanaik, G.Ravindra, C.Sengupta, K.Maithal, P.Balaram, and H.Balaram (2003).
Unusual fluorescence of W168 in Plasmodium falciparum triosephosphate isomerase, probed by single-tryptophan mutants.
  Eur J Biochem, 270, 745-756.  
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
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.  
12006590 K.Maithal, G.Ravindra, H.Balaram, and P.Balaram (2002).
Inhibition of plasmodium falciparum triose-phosphate isomerase by chemical modification of an interface cysteine. Electrospray ionization mass spectrometric analysis of differential cysteine reactivities.
  J Biol Chem, 277, 25106-25114.  
12454456 S.Parthasarathy, H.Balaram, P.Balaram, and M.R.Murthy (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.
PDB codes: 1m7o 1m7p
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, M.T.de 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.  
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
9890931 B.Gopal, S.S.Ray, R.S.Gokhale, H.Balaram, M.R.Murthy, and P.Balaram (1999).
Cavity-creating mutation at the dimer interface of Plasmodium falciparum triosephosphate isomerase: restoration of stability by disulfide cross-linking of subunits.
  Biochemistry, 38, 478-486.  
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
10194326 R.Pérez-Montfort, G.Garza-Ramos, G.H.Alcántara, H.Reyes-Vivas, X.G.Gao, E.Maldonado, M.T.de 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.  
9890925 R.S.Gokhale, S.S.Ray, H.Balaram, and P.Balaram (1999).
Unfolding of Plasmodium falciparum triosephosphate isomerase in urea and guanidinium chloride: evidence for a novel disulfide exchange reaction in a covalently cross-linked mutant.
  Biochemistry, 38, 423-431.  
10467131 S.S.Ray, H.Balaram, and P.Balaram (1999).
Unusual stability of a multiply nicked form of Plasmodium falciparum triosephosphate isomerase.
  Chem Biol, 6, 625-637.  
10468562 X.G.Gao, E.Maldonado, R.Pérez-Montfort, G.Garza-Ramos, M.T.de 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.  
9521758 H.Kim, U.Certa, H.Döbeli, P.Jakob, and W.G.Hol (1998).
Crystal structure of fructose-1,6-bisphosphate aldolase from the human malaria parasite Plasmodium falciparum.
  Biochemistry, 37, 4388-4396.
PDB code: 1a5c
  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.  
9442062 M.Alvarez, J.P.Zeelen, V.Mainfroid, F.Rentier-Delrue, J.A.Martial, L.Wyns, R.K.Wierenga, and D.Maes (1998).
Triose-phosphate isomerase (TIM) of the psychrophilic bacterium Vibrio marinus. Kinetic and structural properties.
  J Biol Chem, 273, 2199-2206.
PDB codes: 1aw1 1aw2
9891808 N.Lang-Unnasch, and A.D.Murphy (1998).
Metabolic changes of the malaria parasite during the transition from the human to the mosquito host.
  Annu Rev Microbiol, 52, 561-590.  
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 codes are shown on the right.