1P2G

Crystal Structure of Glycogen Phosphorylase B in complex with Gamma Cyclodextrin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

The binding of beta- and gamma-cyclodextrins to glycogen phosphorylase b: Kinetic and crystallographic studies.

Pinotsis, N.Leonidas, D.D.Chrysina, E.D.Oikonomakos, N.G.Mavridis, I.M.

(2003) Protein Sci 12: 1914-1924

  • DOI: https://doi.org/10.1110/ps.03149503
  • Primary Citation of Related Structures:  
    1P29, 1P2B, 1P2D, 1P2G

  • PubMed Abstract: 

    A number of regulatory binding sites of glycogen phosphorylase (GP), such as the catalytic, the inhibitor, and the new allosteric sites are currently under investigation as targets for inhibition of hepatic glycogenolysis under high glucose concentrations; in some cases specific inhibitors are under evaluation in human clinical trials for therapeutic intervention in type 2 diabetes. In an attempt to investigate whether the storage site can be exploited as target for modulating hepatic glucose production, alpha-, beta-, and gamma-cyclodextrins were identified as moderate mixed-type competitive inhibitors of GPb (with respect to glycogen) with K(i) values of 47.1, 14.1, and 7.4 mM, respectively. To elucidate the structural basis of inhibition, we determined the structure of GPb complexed with beta- and gamma-cyclodextrins at 1.94 A and 2.3 A resolution, respectively. The structures of the two complexes reveal that the inhibitors can be accommodated in the glycogen storage site of T-state GPb with very little change of the tertiary structure and provide a basis for understanding their potency and subsite specificity. Structural comparisons of the two complexes with GPb in complex with either maltopentaose (G5) or maltoheptaose (G7) show that beta- and gamma-cyclodextrins bind in a mode analogous to the G5 and G7 binding with only some differences imposed by their cyclic conformations. It appears that the binding energy for stabilization of enzyme complexes derives from hydrogen bonding and van der Waals contacts to protein residues. The binding of alpha-cyclodextrin and octakis (2,3,6-tri-O-methyl)-gamma-cyclodextrin was also investigated, but none of them was bound in the crystal; moreover, the latter did not inhibit the phosphorylase reaction.


  • Organizational Affiliation

    Institute of Physical Chemistry, National Center for Scientific Research "Demokritos," Athens, Greece.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glycogen phosphorylase, muscle form842Oryctolagus 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
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  • Reference Sequence
Oligosaccharides

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Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
Cyclooctakis-(1-4)-(alpha-D-glucopyranose)
B
8N/A
Glycosylation Resources
GlyTouCan:  G28503YQ
GlyCosmos:  G28503YQ
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PLP
Query on PLP

Download Ideal Coordinates CCD File 
C [auth A]PYRIDOXAL-5'-PHOSPHATE
C8 H10 N O6 P
NGVDGCNFYWLIFO-UHFFFAOYSA-N
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.189 
  • R-Value Observed: 0.189 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.58α = 90
b = 128.58β = 90
c = 116.382γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MAR345data collection
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-09-02
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-25
    Changes: Data collection, Database references, Refinement description, Structure summary