4JIH

Crystal Structure Of AKR1B10 Complexed With NADP+ And Epalrestat

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.153 

Starting Model: experimental
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Literature

Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: Role of Trp112 (Trp111).

Zhang, L., Zhang, H., Zhao, Y., Li, Z., Chen, S., Zhai, J., Chen, Y., Xie, W., Wang, Z., Li, Q., Zheng, X., Hu, X.

(2013) FEBS Lett 587: 3681-3686

  • DOI: https://doi.org/10.1016/j.febslet.2013.09.031
  • Primary Citation of Related Structures:  
    4GQG, 4I5X, 4JIH, 4JII, 4JIR

  • PubMed Abstract: 

    The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation.

    • Organizational Affiliation: 

    School of Pharmaceutical Sciences, Centre for Cellular and Structural Biology of Sun Yat-sen University, Guangzhou 510006, China.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Aldo-keto reductase family 1 member B10318Homo sapiensMutation(s): 0 
Gene Names: AKR1B10, AKR1B11
EC: 1.1.1 (PDB Primary Data), 1.1.1.300 (UniProt), 1.1.1.54 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for O60218 (Homo sapiens)
Explore O60218 
Go to UniProtKB:  O60218
PHAROS:  O60218
GTEx:  ENSG00000198074 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60218
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP
Download Ideal Coordinates CCD File 
C [auth A]NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
EPR
Query on EPR
Download Ideal Coordinates CCD File 
B [auth A]{5-[(2E)-2-methyl-3-phenylprop-2-en-1-ylidene]-4-oxo-2-thioxo-1,3-thiazolidin-3-yl}acetic acid
C15 H13 N O3 S2
CHNUOJQWGUIOLD-KEBJEMEDSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.153 
  • R-Value Observed: 0.153 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 88.963α = 90
b = 88.963β = 90
c = 77.822γ = 120
Software Package:
Software NamePurpose
CrysalisProdata collection
MOLREPphasing
PHENIXrefinement
CrysalisProdata reduction
SCALAdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-23
    Type: Initial release
  • Version 1.1: 2013-11-27
    Changes: Database references
  • Version 1.2: 2018-01-24
    Changes: Structure summary
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-12-06
    Changes: Data collection
  • Version 1.5: 2024-11-06
    Changes: Structure summary