PDBsum entry 1c8l

Transferase

PDB id

1c8l

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Contents

			Protein chain

					812 a.a. *

			Ligands

					PLP


					BIN


					CFF


					GOL

			Waters ×704

* Residue conservation analysis

PDB id:

1c8l

Links

Name:

Transferase

Title:

Synergistic inhibition of glycogen phosphorylase a by a potential antidiabetic drug and caffeine

Structure:

Protein (glycogen phosphorylase). Chain: a. Ec: 2.4.1.1

Source:

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

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å

R-factor:

0.210

R-free:

0.257

Authors:

K.E.Tsitsanou,V.T.Skamnaki,N.G.Oikonomakos

Key ref:

K.E.Tsitsanou et al. (2000). Structural basis of the synergistic inhibition of glycogen phosphorylase a by caffeine and a potential antidiabetic drug. Arch Biochem Biophys, 384, 245-254. PubMed id: 11368311 DOI: 10.1006/abbi.2000.2121

Date:

16-May-00

Release date:

31-May-00

PROCHECK

	Headers

	References

Protein chain

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

Seq: Struc:

Seq: Struc:					843 a.a. 812 a.a.

Key:

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class:

E.C.2.4.1.1 - glycogen phosphorylase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

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 = PLP)
matches with 63.16% similarity

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

Added reference

DOI no: 10.1006/abbi.2000.2121	Arch Biochem Biophys 384:245-254 (2000)
PubMed id: 11368311

Structural basis of the synergistic inhibition of glycogen phosphorylase a by caffeine and a potential antidiabetic drug.
K.E.Tsitsanou, V.T.Skamnaki, N.G.Oikonomakos.

ABSTRACT

Caffeine, an allosteric inhibitor of glycogen phosphorylase a (GPa), has been shown to act synergistically with the potential antidiabetic drug (-)(S)-3-isopropyl 4-(2-chlorophenyl)-1,4-dihydro-1-ethyl-2-methyl-pyridine-3,5,6-tricarboxylate (W1807). The structure of GPa complexed with caffeine and W1807 has been determined at 100K to 2.3 A resolution, and refined to a crystallographic R value of 0.210 (Rfree = 0.257). The complex structure provides a rationale to understand the structural basis of the synergistic inhibition between W1807 and caffeine. W1807 binds tightly at the allosteric site, and induces substantial conformational changes both in the vicinity of the allosteric site and the subunit interface which transform GPa to the T'-like state conformation already observed with GPa-glucose-W1807 complex. A disordering of the N-terminal tail occurs, while the loop of polypeptide chain containing residues 192-196 and residues 43'-49', from the symmetry related subunit, shift to accommodate W1807. Caffeine binds at the purine inhibitor site by intercalating between the two aromatic rings of Phe285 and Tyr613 and stabilises the location of the 280s loop in the T state conformation.

Literature references that cite this PDB file's key reference

PubMed id

Reference

18041758

K.M.Alexacou, J.M.Hayes, C.Tiraidis, S.E.Zographos, D.D.Leonidas, E.D.Chrysina, G.Archontis, N.G.Oikonomakos, J.V.Paul, B.Varghese, and D.Loganathan (2008).
Crystallographic and computational studies on 4-phenyl-N-(beta-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: comparison with alpha-D-glucose, N-acetyl-beta-D-glucopyranosylamine and N-benzoyl-N'-beta-D-glucopyranosyl urea binding.

Proteins, 71, 1307-1323.

PDB codes:

2pyd 2pyi

17600143

C.Tiraidis, K.M.Alexacou, S.E.Zographos, D.D.Leonidas, T.Gimisis, and N.G.Oikonomakos (2007).
FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase.

Protein Sci, 16, 1773-1782.

PDB code:

2off

16691548

C.Cuadri-Tomé, C.Barón, V.Jara-Pérez, A.Parody-Morreale, J.C.Martinez, and A.Cámara-Artigas (2006).
Kinetic analysis and modelling of the allosteric behaviour of liver and muscle glycogen phosphorylases.

J Mol Recognit, 19, 451-457.

16523484

C.M.Lukacs, N.G.Oikonomakos, R.L.Crowther, L.N.Hong, R.U.Kammlott, W.Levin, S.Li, C.M.Liu, D.Lucas-McGady, S.Pietranico, and L.Reik (2006).
The crystal structure of human muscle glycogen phosphorylase a with bound glucose and AMP: an intermediate conformation with T-state and R-state features.

Proteins, 63, 1123-1126.

PDB code:

1z8d

16371327

F.Magkos, and S.A.Kavouras (2005).
Caffeine use in sports, pharmacokinetics in man, and cellular mechanisms of action.

Crit Rev Food Sci Nutr, 45, 535-562.

15153119

M.N.Kosmopoulou, D.D.Leonidas, E.D.Chrysina, N.Bischler, G.Eisenbrand, C.E.Sakarellos, R.Pauptit, and N.G.Oikonomakos (2004).
Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex.

Eur J Biochem, 271, 2280-2290.

PDB code:

1uzu

12204691

J.L.Ekstrom, T.A.Pauly, M.D.Carty, W.C.Soeller, J.Culp, D.E.Danley, D.J.Hoover, J.L.Treadway, E.M.Gibbs, R.J.Fletterick, Y.S.Day, D.G.Myszka, and V.L.Rath (2002).
Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase.

Chem Biol, 9, 915-924.

PDB codes:

1l5q 1l5r 1l5s 1l7x

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.