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PDBsum entry 1iih

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Isomerase PDB id
1iih
Jmol
Contents
Protein chains
249 a.a. *
Ligands
3PG
Waters ×155
* Residue conservation analysis
PDB id:
1iih
Name: Isomerase
Title: Structure of trypanosoma brucei brucei triosephosphate isomerase complexed with 3-phosphoglycerate
Structure: Triosephosphate isomerase. Chain: a, b. Ec: 5.3.1.1
Source: Trypanosoma brucei brucei. Organism_taxid: 5702. Strain: brucei
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.140    
Authors: M.E.Noble,R.K.Wierenga,A.M.Lambeir,F.R.Opperdoes, A.M.Thunnissen,K.H.Kalk,H.Groendijk,W.G.J.Hol
Key ref: M.E.Noble et al. (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. PubMed id: 2062828
Date:
23-Apr-01     Release date:   11-May-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04789  (TPIS_TRYBB) -  Triosephosphate isomerase, glycosomal
Seq:
Struc:
250 a.a.
249 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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 = 3PG)
matches with 90.00% similarity
= glycerone phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     glycosome   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
Proteins 10:50-69 (1991)
PubMed id: 2062828  
 
 
The adaptability of the active site of trypanosomal triosephosphate isomerase as observed in the crystal structures of three different complexes.
M.E.Noble, R.K.Wierenga, A.M.Lambeir, F.R.Opperdoes, A.M.Thunnissen, K.H.Kalk, H.Groendijk, W.G.Hol.
 
  ABSTRACT  
 
Crystals of triosephosphate isomerase from Trypanosoma brucei brucei have been used in binding studies with three competitive inhibitors of the enzyme's activity. Highly refined structures have been deduced for the complexes between trypanosomal triosephosphate isomerase and a substrate analogue (glycerol-3-phosphate to 2.2 A), a transition state analogue (3-phosphonopropionic acid to 2.6 A), and a compound structurally related to both (3-phosphoglycerate to 2.2 A). The active site structures of these complexes were compared with each other, and with two previously determined structures of triosephosphate isomerase either free from inhibitor or complexed with sulfate. The comparison reveals three conformations available to the "flexible loop" near the active site of triosephosphate isomerase: open (no ligand), almost closed (sulfate), and fully closed (phosphate/phosphonate complexes). Also seen to be sensitive to the nature of the active site ligand is the catalytic residue Glu-167. The side chain of this residue occupies one of two discrete conformations in each of the structures so far observed. A "swung out" conformation unsuitable for catalysis is observed when sulfate, 3-phosphoglycerate, or no ligand is bound, while a "swung in" conformation ideal for catalysis is observed in the complexes with glycerol-3-phosphate or 3-phosphonopropionate. The water structure of the active site is different in all five structures. The results are discussed with respect to the triosephosphate isomerase structure function relationship, and with respect to an on-going drug design project aimed at the selective inhibition of glycolytic enzymes of T. brucei.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20919991 X.Zhang, Y.B.Teng, J.P.Liu, Y.X.He, K.Zhou, Y.Chen, and C.Z.Zhou (2010).
Structural insights into the catalytic mechanism of the yeast pyridoxal 5-phosphate synthase Snz1.
  Biochem J, 432, 445-450.
PDB codes: 3o05 3o06 3o07
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.  
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.  
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.  
15911615 J.Zhu, J.W.Burgner, E.Harms, B.R.Belitsky, and J.L.Smith (2005).
A new arrangement of (beta/alpha)8 barrels in the synthase subunit of PLP synthase.
  J Biol Chem, 280, 27914-27923.
PDB code: 1znn
16159918 L.C.Martin, G.B.Gloor, S.D.Dunn, and L.M.Wahl (2005).
Using information theory to search for co-evolving residues in proteins.
  Bioinformatics, 21, 4116-4124.  
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
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
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
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
11114510 H.Erlandsen, E.E.Abola, and R.C.Stevens (2000).
Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
  Curr Opin Struct Biol, 10, 719-730.  
  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.  
9548921 T.R.Schneider, E.Gerhardt, M.Lee, P.H.Liang, K.S.Anderson, and I.Schlichting (1998).
Loop closure and intersubunit communication in tryptophan synthase.
  Biochemistry, 37, 5394-5406.
PDB codes: 1a50 1a5s 2wsy
  7849584 C.L.Verlinde, E.A.Merritt, F.Van den Akker, H.Kim, I.Feil, L.F.Delboni, S.C.Mande, S.Sarfaty, P.H.Petra, and W.G.Hol (1994).
Protein crystallography and infectious diseases.
  Protein Sci, 3, 1670-1686.  
7922037 C.L.Verlinde, and W.G.Hol (1994).
Structure-based drug design: progress, results and challenges.
  Structure, 2, 577-587.  
  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
  8503454 M.L.Chang, P.J.Artymiuk, X.Wu, S.Hollán, A.Lammi, and L.E.Maquat (1993).
Human triosephosphate isomerase deficiency resulting from mutation of Phe-240.
  Am J Hum Genet, 52, 1260-1269.  
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.  
  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
1624956 C.L.Verlinde, G.Rudenko, and W.G.Hol (1992).
In search of new lead compounds for trypanosomiasis drug design: a protein structure-based linked-fragment approach.
  J Comput Aided Mol Des, 6, 131-147.  
1633802 D.A.Kuntz, R.Osowski, M.Schudok, R.K.Wierenga, K.Müller, H.Kessler, and F.R.Opperdoes (1992).
Inhibition of triosephosphate isomerase from Trypanosoma brucei with cyclic hexapeptides.
  Eur J Biochem, 207, 441-447.  
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.  
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
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.