1AE4

ALDEHYDE REDUCTASE COMPLEXED WITH COFACTOR AND INHIBITOR, ALPHA CARBON ATOMS ONLY


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Studies on the inhibitor-binding site of porcine aldehyde reductase: crystal structure of the holoenzyme-inhibitor ternary complex.

el-Kabbani, O.Carper, D.A.McGowan, M.H.Devedjiev, Y.Rees-Milton, K.J.Flynn, T.G.

(1997) Proteins 29: 186-192

  • DOI: https://doi.org/10.1002/(sici)1097-0134(199710)29:2<186::aid-prot6>3.0.co;2-b
  • Primary Citation of Related Structures:  
    1AE4

  • PubMed Abstract: 

    Aldehyde reductase is an enzyme capable of metabolizing a wide variety of aldehydes to their corresponding alcohols. The tertiary structures of aldehyde reductase and aldose reductase are similar and consist of an alpha/beta-barrel with the active site located at the carboxy terminus of the strands of the barrel. We have determined the X-ray crystal structure of porcine aldehyde reductase holoenzyme in complex with an aldose reductase inhibitor, tolrestat, at 2.4 A resolution to obtain a picture of the binding conformation of inhibitors to aldehyde reductase. Tolrestat binds in the active site pocket of aldehyde reductase and interacts through van der Waals contacts with Arg 312 and Asp 313. The carboxylate group of tolrestat is within hydrogen bonding distance with His 113 and Trp 114. Mutation of Arg 312 to alanine in porcine aldehyde reductase alters the potency of inhibition of the enzyme by aldose reductase inhibitors. Our results indicate that the structure of the inhibitor-binding site of aldehyde reductase differs from that of aldose reductase due to the participation of nonconserved residues in its formation. A major difference is the participation of Arg 312 and Asp 313 in lining the inhibitor-binding site in aldehyde reductase but not in aldose reductase.


  • Organizational Affiliation

    Victorian College of Pharmacy, Department of Medicinal Chemistry, Monash University, Parkville, Australia. ossama@fritz.vcp.monash.edu.au


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ALDEHYDE REDUCTASE325Sus scrofaMutation(s): 0 
EC: 1.1.1.2
UniProt
Find proteins for P50578 (Sus scrofa)
Explore P50578 
Go to UniProtKB:  P50578
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50578
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
TOL
Query on TOL

Download Ideal Coordinates CCD File 
C [auth A]TOLRESTAT
C16 H14 F3 N O3 S
LUBHDINQXIHVLS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TOL Binding MOAD:  1AE4 Ki: 3000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.190 
  • R-Value Observed: 0.190 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.8α = 90
b = 67.8β = 90
c = 245.28γ = 120
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
XENGENdata reduction
X-PLORphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-03-11
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-07
    Changes: Data collection, Database references, Derived calculations, Other