PDBsum entry 2esd

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Oxidoreductase PDB id
Protein chains
474 a.a. *
NAP ×4
G3H ×4
Waters ×776
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of thioacylenzyme intermediate of an NADP dependent aldehyde dehydrogenase
Structure: NADP-dependent glyceraldehyde-3-phosphate dehydrogenase. Chain: a, b, c, d. Synonym: NADP-dependent nonphosphorylating glyceraldehyde- 3-phosphate dehydrogenase. Engineered: yes. Mutation: yes
Source: Streptococcus mutans. Organism_taxid: 1309. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.55Å     R-factor:   0.198     R-free:   0.248
Authors: K.D'Ambrosio,C.Didierjean,E.Benedetti,A.Aubry,C.Corbier
Key ref:
K.D'Ambrosio et al. (2006). The first crystal structure of a thioacylenzyme intermediate in the ALDH family: new coenzyme conformation and relevance to catalysis. Biochemistry, 45, 2978-2986. PubMed id: 16503652 DOI: 10.1021/bi0515117
26-Oct-05     Release date:   02-May-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q59931  (GAPN_STRMU) -  NADP-dependent glyceraldehyde-3-phosphate dehydrogenase
475 a.a.
474 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Glyceraldehyde-3-phosphate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: D-glyceraldehyde 3-phosphate + NADP+ + H2O = 3-phospho-D-glycerate + NADPH
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = G3H)
corresponds exactly
Bound ligand (Het Group name = NAP)
corresponds exactly
+ H(2)O
= 3-phospho-D-glycerate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   2 terms 
  Biochemical function     oxidoreductase activity     3 terms  


DOI no: 10.1021/bi0515117 Biochemistry 45:2978-2986 (2006)
PubMed id: 16503652  
The first crystal structure of a thioacylenzyme intermediate in the ALDH family: new coenzyme conformation and relevance to catalysis.
K.D'Ambrosio, A.Pailot, F.Talfournier, C.Didierjean, E.Benedetti, A.Aubry, G.Branlant, C.Corbier.
Crystal structures of several members of the nonphosphorylating CoA-independent aldehyde dehydrogenase (ALDH) family have shown that the peculiar binding mode of the cofactor to the Rossmann fold results in a conformational flexibility for the nicotinamide moiety of the cofactor. This has been hypothesized to constitute an essential feature of the catalytic mechanism because the conformation of the cofactor required for the acylation step is not appropriate for the deacylation step. In the present study, the structure of a reaction intermediate of the E268A-glyceraldehyde 3-phosphate dehydrogenase (GAPN) from Streptococcus mutans, obtained by soaking the crystals of the enzyme/NADP complex with the natural substrate, is reported. The substrate is bound covalently in the four monomers and presents the geometric characteristics expected for a thioacylenzyme intermediate. Control experiments assessed that reduction of the coenzyme has occurred within the crystal. The structure reveals that reduction of the cofactor upon acylation leads to an extensive motion of the nicotinamide moiety with a flip of the reduced pyridinium ring away from the active site without significant changes of the protein structure. This event positions the reduced nicotinamide moiety in a pocket that likely constitutes the exit door for NADPH. Arguments are provided that the structure reported here constitutes a reasonable picture of the first thioacylenzyme intermediate characterized thus far in the ALDH family and that the position of the reduced nicotinamide moiety observed in GAPN is the one suitable for the deacylation step within all of the nonphosphorylating CoA-independent ALDH family.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19857201 M.Klimacek, and B.Nidetzky (2010).
The oxyanion hole of Pseudomonas fluorescens mannitol 2-dehydrogenase: a novel structural motif for electrostatic stabilization in alcohol dehydrogenase active sites.
  Biochem J, 425, 455-463.  
20062057 S.Perez-Miller, H.Younus, R.Vanam, C.H.Chen, D.Mochly-Rosen, and T.D.Hurley (2010).
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant.
  Nat Struct Mol Biol, 17, 159-164.
PDB codes: 3inj 3inl
21203538 T.Estey, Y.Chen, J.F.Carpenter, and V.Vasiliou (2010).
Structural and functional modifications of corneal crystallin ALDH3A1 by UVB light.
  PLoS One, 5, e15218.  
18611112 S.A.Marchitti, C.Brocker, D.Stagos, and V.Vasiliou (2008).
Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily.
  Expert Opin Drug Metab Toxicol, 4, 697-720.  
17928715 I.Saichana, Y.Ano, O.Adachi, K.Matsushita, and H.Toyama (2007).
Preparation of enzymes required for enzymatic quantification of 5-keto-D-gluconate and 2-keto-D-gluconate.
  Biosci Biotechnol Biochem, 71, 2478-2486.  
17173928 L.Di Costanzo, G.A.Gomez, and D.W.Christianson (2007).
Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and inferences regarding substrate and cofactor specificity.
  J Mol Biol, 366, 481-493.
PDB codes: 2hg2 2ilu 2imp
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.