2INZ

Crystal Structure of Aldose Reductase complexed with 2-Hydroxyphenylacetic Acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.

Brownlee, J.M.Carlson, E.Milne, A.C.Pape, E.Harrison, D.H.

(2006) Bioorg Chem 34: 424-444

  • DOI: https://doi.org/10.1016/j.bioorg.2006.09.004
  • Primary Citation of Related Structures:  
    2INE, 2INZ, 2IPW, 2IQ0, 2IQD, 2IS7, 2ISF

  • PubMed Abstract: 

    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.


  • Organizational Affiliation

    Department of Biochemistry, Medical College of Wiscosin, Milwaukee, WI, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldose reductase315Homo sapiensMutation(s): 0 
Gene Names: AKR1B1ALDR1
EC: 1.1.1.21
UniProt & NIH Common Fund Data Resources
Find proteins for P15121 (Homo sapiens)
Explore P15121 
Go to UniProtKB:  P15121
PHAROS:  P15121
GTEx:  ENSG00000085662 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15121
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
B [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
OHP
Query on OHP

Download Ideal Coordinates CCD File 
C [auth A](2-HYDROXYPHENYL)ACETIC ACID
C8 H8 O3
CCVYRRGZDBSHFU-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
OHP BindingDB:  2INZ Ki: min: 3500, max: 3.20e+4 (nM) from 3 assay(s)
IC50: 3500 (nM) from 1 assay(s)
Binding MOAD:  2INZ Ki: 3500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.228 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.095α = 90
b = 66.899β = 90
c = 92.01γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
X-PLORphasing
X-PLORrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-11-21
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description