PDBsum entry 1n55

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Isomerase PDB id
Protein chain
249 a.a. *
ACY ×2
GOL ×3
Waters ×562
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: 0.83a resolution structure of the e65q mutant of leishmania triosephosphate isomerase complexed with 2-phosphoglycolate
Structure: Triosephosphate isomerase. Chain: a. Synonym: tim. Engineered: yes. Mutation: yes
Source: Leishmania mexicana. Organism_taxid: 5665. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
0.83Å     R-factor:   0.095     R-free:   0.108
Authors: I.Kursula,R.K.Wierenga
Key ref:
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. PubMed id: 12522213 DOI: 10.1074/jbc.M211389200
04-Nov-02     Release date:   21-Jan-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P48499  (TPIS_LEIME) -  Triosephosphate isomerase
251 a.a.
249 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.  - 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 72.73% similarity
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   3 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  


    Added reference    
DOI no: 10.1074/jbc.M211389200 J Biol Chem 278:9544-9551 (2003)
PubMed id: 12522213  
Crystal structure of triosephosphate isomerase complexed with 2-phosphoglycolate at 0.83-A resolution.
I.Kursula, R.K.Wierenga.
The atomic resolution structure of Leishmania mexicana triosephosphate isomerase complexed with 2-phosphoglycolate shows that this transition state analogue is bound in two conformations. Also for the side chain of the catalytic glutamate, Glu(167), two conformations are observed. In both conformations, a very short hydrogen bond exists between the carboxylate group of the ligand and the catalytic glutamate. The distance between O11 of PGA and Oepsilon2 of Glu(167) is 2.61 and 2.55 A for the major and minor conformations, respectively. In either conformation, Oepsilon1 of Glu(167) is hydrogen-bonded to a water network connecting the side chain with bulk solvent. This network also occurs in two mutually exclusive arrangements. Despite the structural disorder in the active site, the C termini of the beta strands that construct the active site display the least anisotropy compared with the rest of the protein. The loops following these beta strands display various degrees of anisotropy, with the tip of the dimer interface loop 3 having very low anisotropy and the C-terminal region of the active site loop 6 having the highest anisotropy. The pyrrolidine ring of Pro(168) at the N-terminal region of loop 6 is in a strained planar conformation to facilitate loop opening and product release.
  Selected figure(s)  
Figure 5.
Fig. 5. Anisotropy in the active site. A, not much anisotropic movement is observed looking approximately along the plane of His95 and the carboxyl group of PGA. B, viewing 90° degrees away, the directional movement of the His95 ring can be seen. Also the Glu167 side chain and the carboxylate group of PGA are anisotropic. For clarity, only the major conformations of Glu167 and PGA are shown. The figure was generated using ORTEP (29).
Figure 6.
Fig. 6. Schematic diagram concerning the active-site geometry of the major conformations of PGA and Glu167. Important hydrogen-bonding interactions are highlighted, including all hydrogen-bonding contacts between the ligand and protein atoms. The numbers refer to distances (Å) in the major conformations of the active-site residues and the ligand. Thr75* is in loop 3 of the adjacent subunit. The red dotted lines describe the interactions between PGA and side-chain atoms, the blue lines represent interactions between PGA and water molecules, and the green lines represent interactions between PGA and main-chain atoms. All other hydrogen bonds are shown in black. The indicated protonation states of the His95, Cys126, Glu167, and PGA are discussed in the text.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 9544-9551) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308811 I.Pápai, A.Hamza, P.M.Pihko, and R.K.Wierenga (2011).
Stereoelectronic requirements for optimal hydrogen-bond-catalyzed enolization.
  Chemistry, 17, 2859-2866.  
  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
20693693 M.Salin, E.G.Kapetaniou, M.Vaismaa, M.Lajunen, M.G.Casteleijn, P.Neubauer, L.Salmon, and R.K.Wierenga (2010).
Crystallographic binding studies with an engineered monomeric variant of triosephosphate isomerase.
  Acta Crystallogr D Biol Crystallogr, 66, 934-944.
PDB codes: 2x16 2x1r 2x1s 2x1t 2x1u 2x2g
20694739 R.K.Wierenga, E.G.Kapetaniou, and R.Venkatesan (2010).
Triosephosphate isomerase: a highly evolved biocatalyst.
  Cell Mol Life Sci, 67, 3961-3982.  
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.  
18300228 C.A.Reyes-López, E.González-Mondragón, C.G.Benítez-Cardoza, M.E.Chánez-Cárdenas, N.Cabrera, R.Pérez-Montfort, and A.Hernández-Arana (2008).
The conserved salt bridge linking two C-terminal beta/alpha units in homodimeric triosephosphate isomerase determines the folding rate of the monomer.
  Proteins, 72, 972-979.  
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
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.  
17578921 L.M.Merlo, M.Lunzer, and A.M.Dean (2007).
An empirical test of the concomitantly variable codon hypothesis.
  Proc Natl Acad Sci U S A, 104, 10938-10943.  
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.  
17623846 T.Prakash, K.S.Sandhu, N.K.Singh, Y.Bhasin, C.Ramakrishnan, and S.K.Brahmachari (2007).
Structural assessment of glycyl mutations in invariantly conserved motifs.
  Proteins, 69, 617-632.  
16941209 B.Rathinasabapathi, S.Wu, S.Sundaram, J.Rivoal, M.Srivastava, and L.Q.Ma (2006).
Arsenic resistance in Pteris vittata L.: identification of a cytosolic triosephosphate isomerase based on cDNA expression cloning in Escherichia coli.
  Plant Mol Biol, 62, 845-857.  
16978361 D.Mathur, G.Malik, and L.C.Garg (2006).
Biochemical and functional characterization of triosephosphate isomerase from Mycobacterium tuberculosis H37Rv.
  FEMS Microbiol Lett, 263, 229-235.  
16323206 F.A.Konuklar, V.Aviyente, and T.Haliloğlu (2006).
Coupling of structural fluctuations to deamidation reaction in triosephosphate isomerase by Gaussian network model.
  Proteins, 62, 715-727.  
16741995 S.Donnini, G.Groenhof, R.K.Wierenga, and A.H.Juffer (2006).
The planar conformation of a strained proline ring: a QM/MM study.
  Proteins, 64, 700-710.  
15890082 D.La, and D.R.Livesay (2005).
Predicting functional sites with an automated algorithm suitable for heterogeneous datasets.
  BMC Bioinformatics, 6, 116.  
15860561 K.Wang, and R.Samudrala (2005).
FSSA: a novel method for identifying functional signatures from structural alignments.
  Bioinformatics, 21, 2969-2977.  
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.  
14675549 A.Vrielink, and N.Sampson (2003).
Sub-Angstrom resolution enzyme X-ray structures: is seeing believing?
  Curr Opin Struct Biol, 13, 709-715.  
14675548 B.W.Dijkstra, and R.G.Matthews (2003).
Catalysis and regulation - from structure to function.
  Curr Opin Struct Biol, 13, 706-708.  
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.