PDBsum entry 2j8t

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protein ligands links
Oxidoreductase PDB id
Protein chain
316 a.a. *
FLC ×2
Waters ×514
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Human aldose reductase in complex with NADP and citrate at 0.82 angstrom
Structure: Aldo-keto reductase family 1, member b1. Chain: a. Synonym: aldose reductase, ctcl tumor antigen hd-cl-07, aldose reductase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
0.82Å     R-factor:   0.099     R-free:   0.112
Authors: M.Biadene,I.Hazemann,A.Cousido,S.Ginell,G.M.Sheldrick, A.Podjarny,T.R.Schneider
Key ref:
M.Biadene et al. (2007). The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop. Acta Crystallogr D Biol Crystallogr, 63, 665-672. PubMed id: 17505104 DOI: 10.1107/S0907444907011997
27-Oct-06     Release date:   29-May-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15121  (ALDR_HUMAN) -  Aldose reductase
316 a.a.
316 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.  - Aldehyde reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Alditol + NAD(P)(+) = aldose + NAD(P)H
Bound ligand (Het Group name = NAP)
corresponds exactly
= aldose
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   5 terms 
  Biological process     small molecule metabolic process   8 terms 
  Biochemical function     electron carrier activity     5 terms  


DOI no: 10.1107/S0907444907011997 Acta Crystallogr D Biol Crystallogr 63:665-672 (2007)
PubMed id: 17505104  
The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop.
M.Biadene, I.Hazemann, A.Cousido, S.Ginell, A.Joachimiak, G.M.Sheldrick, A.Podjarny, T.R.Schneider.
The crystal structure of human aldose reductase in complex with citrate has been determined to a resolution of 0.82 A. The difference electron density for H atoms unequivocally shows that the cofactor is in the oxidized state corresponding to the situation after the catalytic event has occurred. A citrate molecule bound to the active site has been modelled in two different conformations. These two conformations correlate with a fully closed and a partially open conformation of the so-called safety-belt loop (Gly213-Ser226). The open conformation is observed for the first time with the cofactor bound to the protein and may be related to the initial phase of the opening of the safety belt. The structure suggests that after the catalytic event, a rearrangement of a bound ligand can trigger the opening of the safety-belt loop, thus initiating the release of the oxidized cofactor.
  Selected figure(s)  
Figure 2.
Figure 2 Different conformations of the safety-belt loop. The closed and open conformations of the present model are shown in red and yellow (regions for which both conformers are identical are coloured orange), while the open conformation found in the structure of the R298A mutant apo-AR (PDB code 1xgd ) is shown in green. For all conformers the side chain of Trp219 is shown. The cofactor is depicted in blue.
Figure 4.
Figure 4 Electron-density map for the safety-belt loop. Residues Gly213-Leu227 of the major conformation are shown in grey; residues Asp216-Trp219 of the minor conformation are shown in yellow. The [A]-weighted 2mF[o] - DF[c] difference electron density contoured at 1 and the F[o] - F[c] difference electron density contoured at 2 (after omitting the minor conformation from the model, see §-2 for details) are plotted in blue and green.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 665-672) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18300247 J.G.Olsen, L.Pedersen, C.L.Christensen, O.Olsen, and A.Henriksen (2008).
Barley aldose reductase: structure, cofactor binding, and substrate recognition in the aldo/keto reductase 4C family.
  Proteins, 71, 1572-1581.
PDB codes: 2bgq 2bgs 2vdg
  18007059 E.Kiyota, Sousa, M.L.Dos Santos, A.da Costa Lima, M.Menossi, J.A.Yunes, and R.Aparicio (2007).
Crystallization and preliminary X-ray diffraction analysis of maize aldose reductase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 990-992.  
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