1GGN: Structures Of Glycogen Phosphorylase-Inhibitor Complexes And The Implications For Structure-Based Drug Design

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.
PDB ID: 1GGNDownload
MMDB ID: 14430
PDB Deposition Date: 2000/8/29
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.36  Å
Source Organism:
Similar Structures:
Biological Unit for 1GGN: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1GGN
Label Count Molecule
Proteins (2 molecules)
Protein (Glycogen Phosphorylase)(Gene symbol: PYGM)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB