3H1V

Human glucokinase in complex with a synthetic activator

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.235 

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This is version 1.4 of the entry. See complete history. 


Literature

The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators.

Takahashi, K., Hashimoto, N., Nakama, C., Kamata, K., Sasaki, K., Yoshimoto, R., Ohyama, S., Hosaka, H., Maruki, H., Nagata, Y., Eiki, J., Nishimura, T.

(2009) Bioorg Med Chem 17: 7042-7051

  • DOI: https://doi.org/10.1016/j.bmc.2009.05.037
  • Primary Citation of Related Structures:  
    3H1V

  • PubMed Abstract: 

    The optimization of a series of benzimidazole glucokinase activators is described. We identified a novel and potent achiral benzimidazole derivative as an allosteric GK activator. This activator was designed and synthesized via removal of the chiral center of the lead compound, 6-(N-acylpyrrolidin-2-yl)benzimidazole. The activator exhibited good PK profiles in rats and dogs, and significant hypoglycemic efficacy at 1 mg/kg po dosing in a rat OGTT model. The binding site and binding mode of the benzimidazole class of GKA with GK protein was confirmed by X-ray crystallographic analysis.

    • Organizational Affiliation: 

    Banyu Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, 3 Okubo, Tsukuba, Ibaraki 300-2611, Japan. g94e079@ruri.waseda.jp


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GlucokinaseA [auth X]451Homo sapiensMutation(s): 0 
Gene Names: GCK
EC: 2.7.1.2
UniProt & NIH Common Fund Data Resources
Find proteins for P35557 (Homo sapiens)
Explore P35557 
Go to UniProtKB:  P35557
PHAROS:  P35557
GTEx:  ENSG00000106633 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35557
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TK1
Query on TK1
Download Ideal Coordinates CCD File 
C [auth X]1-({5-[4-(methylsulfonyl)phenoxy]-2-pyridin-2-yl-1H-benzimidazol-6-yl}methyl)pyrrolidine-2,5-dione
C24 H20 N4 O5 S
IPZLCOKXDRIZBC-UHFFFAOYSA-N
GLC
Query on GLC
Download Ideal Coordinates CCD File 
B [auth X]alpha-D-glucopyranose
C6 H12 O6
WQZGKKKJIJFFOK-DVKNGEFBSA-N
NA
Query on NA
Download Ideal Coordinates CCD File 
D [auth X]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.11 Å
  • R-Value Free: 0.284 
  • R-Value Work: 0.232 
  • R-Value Observed: 0.235 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.793α = 90
b = 79.793β = 90
c = 326.124γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-10-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2024-03-20
    Changes: Data collection, Database references, Structure summary