PDBsum entry 1lwn

Transferase

PDB id: 1lwn

Contents

Protein chain

815 a.a. *

Ligands

GLC

PLP

Waters ×327

* Residue conservation analysis

PDB id:

1lwn

Name:

Transferase

Title:

Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 a resolution

Structure:

Glycogen phosphorylase. Chain: a. Synonym: myophosphorylase. Ec: 2.4.1.1

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Tissue: muscle

Biol. unit:

Dimer (from PDB file)

Resolution:

2.00Å R-factor: 0.179 R-free: 0.218

Authors:

N.G.Oikonomakos,E.D.Chrysina,M.Kosmopoulou,D.D.Leonidas

Key ref:

N.G.Oikonomakos et al. (2003). Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution. Biochim Biophys Acta, 1647, 325-332. PubMed id: 12686153 DOI: 10.1016/S1570-9639(03)00085-2

Date:

01-Jun-02 Release date: 19-Jun-02

Protein chain

P00489  (PYGM_RABIT) -  Glycogen phosphorylase, muscle form from Oryctolagus cuniculus

Seq: 843 a.a.

Struc: 815 a.a.

Enzyme reactions

• Enzyme class: E.C.2.4.1.1 - glycogen phosphorylase.
• Pathway: Glycogen
• Reaction: [(1->4)-alpha-D-glucosyl](n) + phosphate = [(1->4)-alpha-D-glucosyl](n-1) + alpha-D-glucose 1-phosphate

[(1->4)-alpha-D-glucosyl](n) + phosphate = [(1->4)-alpha-D-glucosyl](n-1) + alpha-D-glucose 1-phosphate (Bound ligand (Het Group name = GLC) matches with 75.00% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/S1570-9639(03)00085-2

Biochim Biophys Acta 1647:325-332 (2003)

PubMed id: 12686153

Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution.

N.G.Oikonomakos, E.D.Chrysina, M.N.Kosmopoulou, D.D.Leonidas.

ABSTRACT

CP320626 has been identified as a potent inhibitor, synergistic with glucose, of human liver glycogen phosphorylase a (LGPa), a possible target for type 2 diabetes therapy. CP320626 is also a potent inhibitor of human muscle GPa. In order to elucidate the structural basis of the mechanism of CP320626 inhibition, the structures of T state rabbit muscle GPa (MGPa) in complex with glucose and in complex with both glucose and CP320626 were determined at 2.0 A resolution, and refined to crystallographic R values of 0.179 (R(free)=0.218) and 0.207 (R(free)=0.235), respectively. CP320626 binds at the new allosteric site, some 33 A from the catalytic site, where glucose binds. The binding of CP320626 to MGPa does not promote extensive conformational changes except for small shifts of the side chain atoms of residues R60, V64, and K191. Both CP320626 and glucose promote the less active T state, while structural comparisons of MGPa-glucose-CP320626 complex with LGPa complexed with a related compound (CP403700) and a glucose analogue inhibitor indicate that the residues of the new allosteric site, conserved in the two isozymes, show no significant differences in their positions.