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PDBsum entry 2prj
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Transferase PDB id
2prj

 

 

 

 

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Contents
Protein chain
830 a.a. *
Ligands
NBG
PLP
IMP
Waters ×259
* Residue conservation analysis
PDB id:
2prj
Name: Transferase
Title: Binding of n-acetyl-beta-d-glucopyranosylamine to glycogen phosphorylase b
Structure: 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:   0.181     R-free:   0.237
Authors: N.G.Oikonomakos,M.Kontou,S.E.Zographos,K.A.Watson,L.N.Johnson, C.J.F.Bichard,G.W.J.Fleet,K.R.Acharya
Key ref: N.G.Oikonomakos et al. (1995). N-acetyl-beta-D-glucopyranosylamine: a potent T-state inhibitor of glycogen phosphorylase. A comparison with alpha-D-glucose. Protein Sci, 4, 2469-2477. PubMed id: 8580837 DOI: 10.1002/pro.5560041203
Date:
29-Dec-99     Release date:   16-Dec-98    
Supersedes: 1prj
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00489  (PYGM_RABIT) -  Glycogen phosphorylase, muscle form from Oryctolagus cuniculus
Seq:
Struc: 		 
Seq:
Struc: 		843 a.a.
830 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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 = IMP)
matches with 50.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1002/pro.5560041203 Protein Sci 4:2469-2477 (1995)
PubMed id: 8580837  
 
 
N-acetyl-beta-D-glucopyranosylamine: a potent T-state inhibitor of glycogen phosphorylase. A comparison with alpha-D-glucose.
N.G.Oikonomakos, M.Kontou, S.E.Zographos, K.A.Watson, L.N.Johnson, C.J.Bichard, G.W.Fleet, K.R.Acharya.
 
  ABSTRACT  
 
Structure-based drug design has led to the discovery of a number of glucose analogue inhibitors of glycogen phosphorylase that have an increased affinity compared to alpha-D-glucose (Ki = 1.7 mM). The best inhibitor in the class of N-acyl derivatives of beta-D-glucopyranosylamine, N-acetyl-beta-D-glucopyranosylamine (1-GlcNAc), has been characterized by kinetic, ultracentrifugation, and crystallographic studies. 1-GlcNAc acts as a competitive inhibitor for both the b (Ki = 32 microM) and the a (Ki = 35 microM) forms of the enzyme with respect to glucose 1-phosphate and in synergism with caffeine, mimicking the binding of glucose. Sedimentation velocity experiments demonstrated that 1-GlcNAc was able to induce dissociation of tetrameric phosphorylase a and stabilization of the dimeric T-state conformation. Co-crystals of the phosphorylase b-1-GlcNAc-IMP complex were grown in space group P4(3)2(1)2, with native-like unit cell dimensions, and the complex structure has been refined to give a crystallographic R factor of 18.1%, for data between 8 and 2.3 A resolution. 1-GlcNAc binds tightly at the catalytic site of T-state phosphorylase b at approximately the same position as that of alpha-D-glucose. The ligand can be accommodated in the catalytic site with very little change in the protein structure and stabilizes the T-state conformation of the 280s loop by making several favorable contacts to Asn 284 of this loop. Structural comparisons show that the T-state phosphorylase b-1-GlcNAc-IMP complex structure is overall similar to the T-state phosphorylase b-alpha-D-glucose complex structure. The structure of the 1-GlcNAc complex provides a rational for the biochemical properties of the inhibitor.
 

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
16616506 E.I.Petsalakis, E.D.Chrysina, C.Tiraidis, T.Hadjiloi, D.D.Leonidas, N.G.Oikonomakos, U.Aich, B.Varghese, and D.Loganathan (2006).
Crystallographic studies on N-azidoacetyl-beta-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D-glucopyranosylamine.
  Bioorg Med Chem, 14, 5316-5324.
PDB code: 2ffr
16464598 T.Hadjiloi, C.Tiraidis, E.D.Chrysina, D.D.Leonidas, N.G.Oikonomakos, P.Tsipos, and T.Gimisis (2006).
Binding of oxalyl derivatives of beta-d-glucopyranosylamine to muscle glycogen phosphorylase b.
  Bioorg Med Chem, 14, 3872-3882.
PDB codes: 2f3p 2f3q 2f3s 2f3u
15741340 E.D.Chrysina, M.N.Kosmopoulou, C.Tiraidis, R.Kardakaris, N.Bischler, D.D.Leonidas, Z.Hadady, L.Somsak, T.Docsa, P.Gergely, and N.G.Oikonomakos (2005).
Kinetic and crystallographic studies on 2-(beta-D-glucopyranosyl)-5-methyl-1, 3, 4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site.
  Protein Sci, 14, 873-888.
PDB codes: 1xkx 1xl0 1xl1
16222658 K.A.Watson, E.D.Chrysina, K.E.Tsitsanou, S.E.Zographos, G.Archontis, G.W.Fleet, and N.G.Oikonomakos (2005).
Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase.
  Proteins, 61, 966-983.
PDB codes: 1fs4 1ftq 1ftw 1fty 1fu4 1fu7 1fu8
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
11895439 N.G.Oikonomakos, M.Kosmopoulou, S.E.Zographos, D.D.Leonidas, E.D.Chrysina, L.Somsák, V.Nagy, J.P.Praly, T.Docsa, B.Tóth, and P.Gergely (2002).
Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies.
  Eur J Biochem, 269, 1684-1696.
PDB codes: 1k06 1k08 1k0q 1kti
10873856 N.G.Oikonomakos, V.T.Skamnaki, K.E.Tsitsanou, N.G.Gavalas, and L.N.Johnson (2000).
A new allosteric site in glycogen phosphorylase b as a target for drug interactions.
  Structure, 8, 575-584.
PDB code: 1c50
10980448 V.L.Rath, M.Ammirati, D.E.Danley, J.L.Ekstrom, E.M.Gibbs, T.R.Hynes, A.M.Mathiowetz, R.K.McPherson, T.V.Olson, J.L.Treadway, and D.J.Hoover (2000).
Human liver glycogen phosphorylase inhibitors bind at a new allosteric site.
  Chem Biol, 7, 677-682.
PDB codes: 1em6 1exv
10949035 V.L.Rath, M.Ammirati, P.K.LeMotte, K.F.Fennell, M.N.Mansour, D.E.Danley, T.R.Hynes, G.K.Schulte, D.J.Wasilko, and J.Pandit (2000).
Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core.
  Mol Cell, 6, 139-148.
PDB codes: 1fa9 1fc0
  10211820 K.E.Tsitsanou, N.G.Oikonomakos, S.E.Zographos, V.T.Skamnaki, M.Gregoriou, K.A.Watson, L.N.Johnson, and G.W.Fleet (1999).
Effects of commonly used cryoprotectants on glycogen phosphorylase activity and structure.
  Protein Sci, 8, 741-749.
PDB codes: 1b4d 1bx3
  10548038 N.G.Oikonomakos, K.E.Tsitsanou, S.E.Zographos, V.T.Skamnaki, S.Goldmann, and H.Bischoff (1999).
Allosteric inhibition of glycogen phosphorylase a by the potential antidiabetic drug 3-isopropyl 4-(2-chlorophenyl)-1,4-dihydro-1-ethyl-2-methyl-pyridine-3,5,6-tricarbo xylate.
  Protein Sci, 8, 1930-1945.
PDB codes: 2gpa 3amv
  9568898 M.Gregoriou, M.E.Noble, K.A.Watson, E.F.Garman, T.M.Krulle, C.de la Fuente, G.W.Fleet, N.G.Oikonomakos, and L.N.Johnson (1998).
The structure of a glycogen phosphorylase glucopyranose spirohydantoin complex at 1.8 A resolution and 100 K: the role of the water structure and its contribution to binding.
  Protein Sci, 7, 915-927.
PDB codes: 1a8i 2gpn
  8976550 N.G.Oikonomakos, S.E.Zographos, K.E.Tsitsanou, L.N.Johnson, and K.R.Acharya (1996).
Activator anion binding site in pyridoxal phosphorylase b: the binding of phosphite, phosphate, and fluorophosphate in the crystal.
  Protein Sci, 5, 2416-2428.
PDB codes: 1skc 1skd 1ske 2skc 2skd 2ske
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.

 

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