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PDBsum entry 1fc0
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1fc0

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
792 a.a. *
Ligands
NBG ×2
PLP ×2
Waters ×255
* Residue conservation analysis
PDB id:
1fc0
Name: Transferase
Title: Human liver glycogen phosphorylase complexed with n-acetyl-beta-d- glucopyranosylamine
Structure: Glycogen phosphorylase, liver form. Chain: a, b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: liver. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.198     R-free:   0.235
Authors: V.L.Rath,M.Ammirati,P.K.Lemotte,K.F.Fennell,M.M.Mansour,D.E.Danley, T.R.Hynes,G.K.Schulte,D.J.Wasilko,J.Pandit
Key ref: V.L.Rath et al. (2000). Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core. Mol Cell, 6, 139-148. PubMed id: 10949035
Date:
17-Jul-00     Release date:   25-Aug-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06737  (PYGL_HUMAN) -  Glycogen phosphorylase, liver form from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		847 a.a.
792 a.a.
Key:    PfamA domain  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    
 
 
Mol Cell 6:139-148 (2000)
PubMed id: 10949035  
 
 
Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core.
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, J.Pandit.
 
  ABSTRACT  
 
Glycogen phosphorylases catalyze the breakdown of glycogen to glucose-1-phosphate, which enters glycolysis to fulfill the energetic requirements of the organism. Maintaining control of blood glucose levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic target. To support inhibitor design, we determined the crystal structures of the active and inactive forms of human liver glycogen phosphorylase a. During activation, forty residues of the catalytic site undergo order/disorder transitions, changes in secondary structure, or packing to reorganize the catalytic site for substrate binding and catalysis. Knowing the inactive and active conformations of the liver enzyme and how each differs from its counterpart in muscle phosphorylase provides the basis for designing inhibitors that bind preferentially to the inactive conformation of the liver isozyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18198182 A.Pautsch, N.Stadler, O.Wissdorf, E.Langkopf, W.Moreth, and R.Streicher (2008).
Molecular recognition of the protein phosphatase 1 glycogen targeting subunit by glycogen phosphorylase.
  J Biol Chem, 283, 8913-8918.
PDB code: 2qll
18518825 L.L.Lairson, B.Henrissat, G.J.Davies, and S.G.Withers (2008).
Glycosyltransferases: structures, functions, and mechanisms.
  Annu Rev Biochem, 77, 521-555.  
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
17705025 N.J.Beauchamp, J.Taybert, M.P.Champion, V.Layet, P.Heinz-Erian, A.Dalton, M.S.Tanner, E.Pronicka, and M.J.Sharrard (2007).
High frequency of missense mutations in glycogen storage disease type VI.
  J Inherit Metab Dis, 30, 722-734.  
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
17016495 S.Freeman, J.B.Bartlett, G.Convey, I.Hardern, J.L.Teague, S.J.Loxham, J.M.Allen, S.M.Poucher, and A.D.Charles (2006).
Sensitivity of glycogen phosphorylase isoforms to indole site inhibitors is markedly dependent on the activation state of the enzyme.
  Br J Pharmacol, 149, 775-785.  
16151135 M.Yanase, H.Takata, K.Fujii, T.Takaha, and T.Kuriki (2005).
Cumulative effect of amino acid replacements results in enhanced thermostability of potato type L alpha-glucan phosphorylase.
  Appl Environ Microbiol, 71, 5433-5439.  
15272305 A.Buschiazzo, J.E.Ugalde, M.E.Guerin, W.Shepard, R.A.Ugalde, and P.M.Alzari (2004).
Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation.
  EMBO J, 23, 3196-3205.
PDB codes: 1rzu 1rzv
14691231 J.Adams, Z.P.Chen, B.J.Van Denderen, C.J.Morton, M.W.Parker, L.A.Witters, D.Stapleton, and B.E.Kemp (2004).
Intrasteric control of AMPK via the gamma1 subunit AMP allosteric regulatory site.
  Protein Sci, 13, 155-165.  
12445771 D.D.Boehr, A.R.Farley, G.D.Wright, and J.R.Cox (2002).
Analysis of the pi-pi stacking interactions between the aminoglycoside antibiotic kinase APH(3')-IIIa and its nucleotide ligands.
  Chem Biol, 9, 1209-1217.  
11340058 J.L.Buchbinder, V.L.Rath, and R.J.Fletterick (2001).
Structural relationships among regulated and unregulated phosphorylases.
  Annu Rev Biophys Biomol Struct, 30, 191-209.  
11227044 J.L.Treadway, P.Mendys, and D.J.Hoover (2001).
Glycogen phosphorylase inhibitors for treatment of type 2 diabetes mellitus.
  Expert Opin Investig Drugs, 10, 439-454.  
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 code is shown on the right.

 

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