PDBsum entry 2ine

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protein ligands links
Oxidoreductase PDB id
Protein chain
314 a.a. *
Waters ×239
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of aldose reductase complexed with phenylacetic acid
Structure: Aldose reductase. Chain: a. Synonym: ar, aldehyde reductase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: akr1b1, aldr1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.90Å     R-factor:   0.178     R-free:   0.226
Authors: D.H.T.Harrison,A.Milne,J.M.Brownlee
Key ref: J.M.Brownlee et al. (2006). Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes. Bioorg Chem, 34, 424-444. PubMed id: 17083960 DOI: 10.1016/j.bioorg.2006.09.004
06-Oct-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15121  (ALDR_HUMAN) -  Aldose reductase
316 a.a.
314 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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: 10.1016/j.bioorg.2006.09.004 Bioorg Chem 34:424-444 (2006)
PubMed id: 17083960  
Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.
J.M.Brownlee, E.Carlson, A.C.Milne, E.Pape, D.H.Harrison.
The competitive inhibition constants of series of inhibitors related to phenylacetic acid against both wild-type and the doubly mutanted C298A/W219Y aldose reductase have been measured. Van't Hoff analysis shows that these acids bind with an enthalpy near -6.8 kcal/mol derived from the electrostatic interactions, while the 100-fold differences in binding affinity appear to be largely due to entropic factors that result from differences in conformational freedom in the unbound state. These temperature studies also point out the difference between substrate and inhibitor binding. X-ray crystallographic analysis of a few of these inhibitor complexes both confirms the importance of a previously described anion binding site and reveals the hydrophobic nature of the primary binding site and its general plasticity. Based on these results, N-glycylthiosuccinimides were synthesized to demonstrate their potential in studies that probe distal binding sites. Reduced alpha-lipoic acid, an anti-oxidant and therapeutic for diabetic complications, was shown to bind aldose reductase with a binding constant of 1 microM.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19275144 C.Mulakala, and Y.N.Kaznessis (2009).
Path-integral method for predicting relative binding affinities of protein-ligand complexes.
  J Am Chem Soc, 131, 4521-4528.  
19514026 S.Kazemi, D.M.Krüger, F.Sirockin, and H.Gohlke (2009).
Elastic potential grids: accurate and efficient representation of intermolecular interactions for fully flexible docking.
  ChemMedChem, 4, 1264-1268.  
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