1HLF

BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Kinetic and crystallographic studies of glucopyranosylidene spirothiohydantoin binding to glycogen phosphorylase B

Oikonomakos, N.G.Skamnaki, V.T.Osz, E.Szilagyi, L.Somsak, L.Docsa, T.Toth, B.Gergely, P.

(2002) Bioorg Med Chem 10: 261-268

  • DOI: https://doi.org/10.1016/s0968-0896(01)00277-2
  • Primary Citation of Related Structures:  
    1GGN, 1HLF

  • PubMed Abstract: 

    Glucopyranosylidene spirothiohydantoin (TH) has been identified as a potential inhibitor of both muscle and liver glycogen phosphorylase b (GPb) and a (GPa) and shown to diminish liver GPa activity in vitro. Kinetic experiments reported here show that TH inhibits muscle GPb competitively with respect to both substrates phosphate (K(i)=2.3 microM) and glycogen (K(i)=2.8 microM). The structure of the GPb-TH complex has been determined at a resolution of 2.26 A and refined to a crystallographic R value of 0.193 (R(free)=0.211). The structure of GPb-TH complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change of the tertiary structure, and provides a basis of understanding potency and specificity of the inhibitor. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the glucose complex, while the rigid thiohydantoin group is in a favourable electrostatic environment and makes additional polar contacts to the protein.


  • Organizational Affiliation

    Institute of Biological Research and Biotechnology, The National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLYCOGEN PHOSPHORYLASE842Oryctolagus cuniculusMutation(s): 0 
EC: 2.4.1.1
UniProt
Find proteins for P00489 (Oryctolagus cuniculus)
Explore P00489 
Go to UniProtKB:  P00489
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00489
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GL4
Query on GL4

Download Ideal Coordinates CCD File 
C [auth A](5S,7R,8S,9S,10R)-8,9,10-trihydroxy-7-(hydroxymethyl)-2-thioxo-6-oxa-1,3-diazaspiro[4.5]decan-4-one
C8 H12 N2 O6 S
OEWLGQKSTDZKFN-WWHASAIZSA-N
PLP
Query on PLP

Download Ideal Coordinates CCD File 
B [auth A]PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
GL4 BindingDB:  1HLF Ki: min: 5100, max: 1.09e+4 (nM) from 3 assay(s)
PDBBind:  1HLF Ki: 2300 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.26 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.787α = 90
b = 128.787β = 90
c = 116.169γ = 90
Software Package:
Software NamePurpose
CCP4model building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
CCP4phasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-12-13
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Derived calculations, Structure summary
  • Version 1.5: 2023-08-09
    Changes: Data collection, Database references, Refinement description, Structure summary