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Oxidoreductase PDB id
1qxs
Jmol
Contents
Protein chains
359 a.a. *
Ligands
NAD ×4
S70
Waters ×453
* Residue conservation analysis
PDB id:
1qxs
Name: Oxidoreductase
Title: Crystal structure of trypanosoma cruzi glyceraldehyde-3- phosphate dehydrogenase complexed with an analogue of 1,3- bisphospho-d-glyceric acid
Structure: Glyceraldehyde 3-phosphate dehydrogenase, glycosomal. Chain: c, d, a, b. Synonym: gapdh. Engineered: yes
Source: Trypanosoma cruzi. Organism_taxid: 5693. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PQS)
Resolution:
2.75Å     R-factor:   0.198     R-free:   0.276
Authors: M.S.Castilho,F.Pavao,G.Oliva
Key ref:
S.Ladame et al. (2003). Crystal structure of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase complexed with an analogue of 1,3-bisphospho-d-glyceric acid. Eur J Biochem, 270, 4574-4586. PubMed id: 14622286 DOI: 10.1046/j.1432-1033.2003.03857.x
Date:
08-Sep-03     Release date:   11-May-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P22513  (G3PG_TRYCR) -  Glyceraldehyde-3-phosphate dehydrogenase, glycosomal
Seq:
Struc: 		359 a.a.
359 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.2.1.12  - Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Glyceraldehyde-3-phosphate Dehydrogenase (phosphorylating)
      Reaction: D-glyceraldehyde 3-phosphate + phosphate + NAD+ = 3-phospho-D-glyceroyl phosphate + NADH
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = S70)
matches with 66.00% similarity 		+ phosphate
 +
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly 		= 3-phospho-D-glyceroyl phosphate
 + NADH
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     oxidation-reduction process   3 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1046/j.1432-1033.2003.03857.x Eur J Biochem 270:4574-4586 (2003)
PubMed id: 14622286  
 
 
Crystal structure of Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase complexed with an analogue of 1,3-bisphospho-d-glyceric acid.
S.Ladame, M.S.Castilho, C.H.Silva, C.Denier, V.Hannaert, J.Périé, G.Oliva, M.Willson.
 
  ABSTRACT  
 
We report here the first crystal structure of a stable isosteric analogue of 1,3-bisphospho-d-glyceric acid (1,3-BPGA) bound to the catalytic domain of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) in which the two phosphoryl moieties interact with Arg249. This complex possibly illustrates a step of the catalytic process by which Arg249 may induce compression of the product formed, allowing its expulsion from the active site. Structural modifications were introduced into this isosteric analogue and the respective inhibitory effects of the resulting diphosphorylated compounds on T. cruzi and Trypanosoma brucei gGAPDHs were investigated by enzymatic inhibition studies, fluorescence spectroscopy, site-directed mutagenesis, and molecular modelling. Despite the high homology between the two trypanomastid gGAPDHs (> 95%), we have identified specific interactions that could be used to design selective irreversible inhibitors against T. cruzi gGAPDH.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. HOP interaction profile in T. cruzi gGAPDH active site. The phosphate moiety hydrogen bonds with Arg249, Thr197 and Thr199 (blue dashed lines). The phosphonate moiety hydrogen bonds to Arg249, Ser247 (blue dashed lines) and its carbonyl group points to His194. Two additional hydrogen bonds are formed with crystallographic water molecules. The protein atoms are depicted as a ribbon tracing except for the catalytic Cys166, His194 and other residues highlighted that interact with HOP. This figure was generated with PYMOL software [44]. 		Figure 4.
Fig. 4. Stereo diagrams of the active sites of T. brucei gGAPDH(A) and T. cruzi gGAPDH(B) containing their respective inhibitors which were superimposed after the minimization protocol. The inhibitors are shown in colours: HOP (yellow), compound 5 (coloured by atoms), compound 6 (cyan), compound 7 (green) and compound 8 (magenta).
 
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2003, 270, 4574-4586) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19243605 W.J.Cook, O.Senkovich, and D.Chattopadhyay (2009).
An unexpected phosphate binding site in glyceraldehyde 3-phosphate dehydrogenase: crystal structures of apo, holo and ternary complex of Cryptosporidium parvum enzyme.
  BMC Struct Biol, 9, 9.
PDB codes: 1vsu 1vsv 3cif
16510976 J.L.Jenkins, and J.J.Tanner (2006).
High-resolution structure of human D-glyceraldehyde-3-phosphate dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 62, 290-301.
PDB codes: 1u8f 2feh
15917890 S.Ladame, R.Fauré, C.Denier, F.Lakhdar-Ghazal, and M.Willson (2005).
Selective inhibition of Trypanosoma cruzi GAPDH by "bi-substrate" analogues.
  Org Biomol Chem, 3, 2070-2072.  
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.