PDBsum entry 3dds

Transferase

PDB id: 3dds

Contents

Protein chain

811 a.a. *

Ligands

NBG ×2

PO4

PLP ×2

CFF ×2

26B ×3

MPD

MES

Waters ×1353

* Residue conservation analysis

PDB id:

3dds

Name:

Transferase

Title:

Crystal structure of glycogen phosphorylase complexed with an anthranilimide based inhibitor gsk261

Structure:

Glycogen phosphorylase, liver form. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Tissue: liver isoform. Gene: pygl. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.80Å R-factor: 0.175 R-free: 0.198

Authors:

R.T.Nolte

Key ref:

S.A.Thomson et al. (2009). Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy. Bioorg Med Chem Lett, 19, 1177-1182. PubMed id: 19138846

Date:

06-Jun-08 Release date: 27-Jan-09

Protein chains

P06737  (PYGL_HUMAN) -  Glycogen phosphorylase, liver form from Homo sapiens

Seq: 847 a.a.

Struc: 811 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 (Bound ligand (Het Group name = PO4) corresponds exactly) = [(1->4)-alpha-D-glucosyl](n-1) + alpha-D-glucose 1-phosphate (Bound ligand (Het Group name = PLP) matches with 63.16% similarity)

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

Added reference

Bioorg Med Chem Lett 19:1177-1182 (2009)

PubMed id: 19138846

Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.

S.A.Thomson, P.Banker, D.M.Bickett, J.A.Boucheron, H.L.Carter, D.C.Clancy, J.P.Cooper, S.H.Dickerson, D.M.Garrido, R.T.Nolte, A.J.Peat, L.R.Sheckler, S.M.Sparks, F.X.Tavares, L.Wang, T.Y.Wang, J.E.Weiel.

ABSTRACT

Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.