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PDBsum entry 1ttj

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Isomerase(intramolecular oxidoreductase) PDB id
1ttj
Jmol
Contents
Protein chain
235 a.a. *
Ligands
PGH
Waters ×40
* Residue conservation analysis
PDB id:
1ttj
Name: Isomerase(intramolecular oxidoreductase)
Title: Three new crystal structures of point mutation variants of monotim: conformational flexibility of loop-1,loop-4 and loop-8
Structure: Triosephosphate isomerase. Chain: a. Mutation: yes
Source: Trypanosoma brucei brucei. Organism_taxid: 5702. Strain: brucei
Resolution:
2.40Å     R-factor:   0.178    
Authors: K.V.Radha Kishan,R.K.Wierenga
Key ref:
T.V.Borchert et al. (1995). Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8. Structure, 3, 669-679. PubMed id: 8591044 DOI: 10.1016/S0969-2126(01)00202-7
Date:
20-Apr-95     Release date:   15-Sep-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04789  (TPIS_TRYBB) -  Triosephosphate isomerase, glycosomal
Seq:
Struc:
250 a.a.
235 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 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 = PGH)
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!
  Cellular component     glycosome   2 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(01)00202-7 Structure 3:669-679 (1995)
PubMed id: 8591044  
 
 
Three new crystal structures of point mutation variants of monoTIM: conformational flexibility of loop-1, loop-4 and loop-8.
T.V.Borchert, K.V.Kishan, J.P.Zeelen, W.Schliebs, N.Thanki, R.Abagyan, R.Jaenicke, R.K.Wierenga.
 
  ABSTRACT  
 
BACKGROUND: Wild-type triosephosphate isomerase (TIM) is a very stable dimeric enzyme. This dimer can be converted into a stable monomeric protein (monoTIM) by replacing the 15-residue interface loop (loop-3) by a shorter, 8-residue, loop. The crystal structure of monoTIM shows that two active-site loops (loop-1 and loop-4), which are at the dimer interface in wild-type TIM, have acquired rather different structural properties. Nevertheless, monoTIM has residual catalytic activity. RESULTS: Three new structures of variants of monoTIM are presented, a double-point mutant crystallized in the presence and absence of bound inhibitor, and a single-point mutant in the presence of a different inhibitor. These new structures show large structural variability for the active-site loops, loop-1, loop-4 and loop-8. In the structures with inhibitor bound, the catalytic lysine (Lys13 in loop-1) and the catalytic histidine (His95 in loop-4) adopt conformations similar to those observed in wild-type TIM, but very different from the monoTIM structure. CONCLUSIONS: The residual catalytic activity of monoTIM can now be rationalized. In the presence of substrate analogues the active-site loops, loop-1, loop-4 and loop-8, as well as the catalytic residues, adopt conformations similar to those seen in the wild-type protein. These loops lack conformational flexibility in wild-type TIM. The data suggest that the rigidity of these loops in wild-type TIM, resulting from subunit-subunit contacts at the dimer interface, is important for optimal catalysis.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. (a) The reaction catalyzed by TIM. (b) The structures of two inhibitors of TIM, PGH and 2PG. Figure 1. (a) The reaction catalyzed by TIM. (b) The structures of two inhibitors of TIM, PGH and 2PG.
Figure 4.
Figure 4. Comparison of monoTIM-SS (red), monoTIM (green) and wtTIM (yellow). (a) The complete Cα traces. One residue of each front loop of monoTIM is labelled: Trp12 (L1), Phe45 (L2), Ala70 (L3), His95 (L4), Glu129 (L5), Val169 (L6), Gly212 (L7) and Gly235 (L8). Also shown, in green, is the sulphate ion, near loop-6, loop-7 and loop-8, as observed in the monoTIM structure. (b) Comparison of the Cα traces near L8, L1, L2 and L3. The side chains of residues Ser237 (L8), Trp12 (L1), Thr44 (L2) and Gln65 (L3) are also shown. Figure 4. Comparison of monoTIM-SS (red), monoTIM (green) and wtTIM (yellow). (a) The complete Cα traces. One residue of each front loop of monoTIM is labelled: Trp12 (L1), Phe45 (L2), Ala70 (L3), His95 (L4), Glu129 (L5), Val169 (L6), Gly212 (L7) and Gly235 (L8). Also shown, in green, is the sulphate ion, near loop-6, loop-7 and loop-8, as observed in the monoTIM structure. (b) Comparison of the Cα traces near L8, L1, L2 and L3. The side chains of residues Ser237 (L8), Trp12 (L1), Thr44 (L2) and Gln65 (L3) are also shown.
 
  The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 669-679) copyright 1995.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
17411375 T.Cardozo, T.Kimura, S.Philpott, B.Weiser, H.Burger, and S.Zolla-Pazner (2007).
Structural basis for coreceptor selectivity by the HIV type 1 V3 loop.
  AIDS Res Hum Retroviruses, 23, 415-426.  
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.  
11151009 B.V.Norledge, A.M.Lambeir, R.A.Abagyan, A.Rottmann, A.M.Fernandez, V.V.Filimonov, M.G.Peter, and R.K.Wierenga (2001).
Modeling, mutagenesis, and structural studies on the fully conserved phosphate-binding loop (loop 8) of triosephosphate isomerase: toward a new substrate specificity.
  Proteins, 42, 383-389.
PDB code: 1dkw
10785370 A.M.Lambeir, J.Backmann, J.Ruiz-Sanz, V.Filimonov, J.E.Nielsen, I.Kursula, B.V.Norledge, and R.K.Wierenga (2000).
The ionization of a buried glutamic acid is thermodynamically linked to the stability of Leishmania mexicana triose phosphate isomerase.
  Eur J Biochem, 267, 2516-2524.
PDB code: 1qds
10745009 R.Thoma, M.Hennig, R.Sterner, and K.Kirschner (2000).
Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima.
  Structure, 8, 265-276.
PDB code: 1dl3
9636063 S.Miller, B.Schuler, and R.Seckler (1998).
A reversibly unfolding fragment of P22 tailspike protein with native structure: the isolated beta-helix domain.
  Biochemistry, 37, 9160-9168.  
  8745400 W.Schliebs, N.Thanki, R.Eritja, and R.Wierenga (1996).
Active site properties of monomeric triosephosphate isomerase (monoTIM) as deduced from mutational and structural studies.
  Protein Sci, 5, 229-239.  
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.