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PDBsum entry 4icd

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protein links
Oxidoreductase (NAD(a)-choh(d)) PDB id
4icd
Jmol
Contents
Protein chain
414 a.a. *
Waters ×143
* Residue conservation analysis
PDB id:
4icd
Name: Oxidoreductase (NAD(a)-choh(d))
Title: Regulation of isocitrate dehydrogenase by phosphorylation in long-range conformational change in the free enzyme
Structure: Phosphorylated isocitrate dehydrogenase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.169    
Authors: J.H.Hurley,A.M.Dean,P.E.Thorsness,D.E.Koshlandjunior,R.M.Str
Key ref: J.H.Hurley et al. (1990). Regulation of isocitrate dehydrogenase by phosphorylation involves no long-range conformational change in the free enzyme. J Biol Chem, 265, 3599-3602. PubMed id: 2406256
Date:
28-Dec-89     Release date:   15-Jan-91    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
Seq:
Struc:
416 a.a.
414 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.42  - Isocitrate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Citric acid cycle
      Reaction: Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH
Isocitrate
+ NADP(+)
= 2-oxoglutarate
+ CO(2)
+ NADPH
      Cofactor: Mn(2+) or Mg(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     oxidoreductase activity     6 terms  

 

 
    reference    
 
 
J Biol Chem 265:3599-3602 (1990)
PubMed id: 2406256  
 
 
Regulation of isocitrate dehydrogenase by phosphorylation involves no long-range conformational change in the free enzyme.
J.H.Hurley, A.M.Dean, P.E.Thorsness, D.E.Koshland, R.M.Stroud.
 
  ABSTRACT  
 
The structure of the phosphorylated form of isocitrate dehydrogenase from Escherichia coli has been solved and refined to an R-factor of 16.9% at 2.5-A resolution. Comparison with the structure of the dephosphorylated enzyme shows that there are no large scale conformational changes and that small conformational changes are highly localized around the site of phosphorylation at serine 113. Tyrosine 160 rotates by 15 degrees, and there is a local rearrangement of water structure. There is an 0.2-A net movement of loop 230-234, and side chain shifts of 0.2 A root mean square for isoleucine 159 and lysine 199. The lack of large conformational changes, the observation of a possible isocitrate binding site close to serine 113, and the demonstration that the phosphorylated enzyme is unable to bind isocitrate suggest that this enzyme is inactivated by a direct electrostatic interaction between the substrate and the serine phosphate.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20513808 Z.J.Reitman, and H.Yan (2010).
Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism.
  J Natl Cancer Inst, 102, 932-941.  
17521420 J.L.Jiménez, B.Hegemann, J.R.Hutchins, J.M.Peters, and R.Durbin (2007).
A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database.
  Genome Biol, 8, R90.  
16362493 I.L.Jung, S.K.Kim, and I.G.Kim (2006).
The RpoS-mediated regulation of isocitrate dehydrogenase gene expression in Escherichia coli.
  Curr Microbiol, 52, 21-26.  
16171520 A.Krupa, and N.Srinivasan (2005).
Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes.
  BMC Genomics, 6, 129.  
15517599 G.E.Parker, B.E.West, F.A.Witzmann, and S.J.Rhodes (2005).
Serine/threonine/tyrosine phosphorylation of the LHX3 LIM-homeodomain transcription factor.
  J Cell Biochem, 94, 67-80.  
15937189 W.K.Ray, S.M.Keith, A.M.DeSantis, J.P.Hunt, T.J.Larson, R.F.Helm, and P.J.Kennelly (2005).
A phosphohexomutase from the archaeon Sulfolobus solfataricus is covalently modified by phosphorylation on serine.
  J Bacteriol, 187, 4270-4275.  
12694190 C.Wrenger, and S.Müller (2003).
Isocitrate dehydrogenase of Plasmodium falciparum.
  Eur J Biochem, 270, 1775-1783.  
12218169 M.L.Baker, I.I.Serysheva, S.Sencer, Y.Wu, S.J.Ludtke, W.Jiang, S.L.Hamilton, and W.Chiu (2002).
The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
  Proc Natl Acad Sci U S A, 99, 12155-12160.  
10677231 C.Weiss, Y.Zeng, J.Huang, M.B.Sobocka, and J.I.Rushbrook (2000).
Bovine NAD+-dependent isocitrate dehydrogenase: alternative splicing and tissue-dependent expression of subunit 1.
  Biochemistry, 39, 1807-1816.  
9891796 A.J.Cozzone (1998).
Regulation of acetate metabolism by protein phosphorylation in enteric bacteria.
  Annu Rev Microbiol, 52, 127-164.  
9783749 B.L.Stoddard, B.E.Cohen, M.Brubaker, A.D.Mesecar, and D.E.Koshland (1998).
Millisecond Laue structures of an enzyme-product complex using photocaged substrate analogs.
  Nat Struct Biol, 5, 891-897.
PDB code: 1bl5
9818266 B.L.Stoddard (1998).
New results using Laue diffraction and time-resolved crystallography.
  Curr Opin Struct Biol, 8, 612-618.  
9548941 M.Schutkowski, A.Bernhardt, X.Z.Zhou, M.Shen, U.Reimer, J.U.Rahfeld, K.P.Lu, and G.Fischer (1998).
Role of phosphorylation in determining the backbone dynamics of the serine/threonine-proline motif and Pin1 substrate recognition.
  Biochemistry, 37, 5566-5575.  
9220992 B.E.Cohen, B.L.Stoddard, and D.E.Koshland (1997).
Caged NADP and NAD. Synthesis and characterization of functionally distinct caged compounds.
  Biochemistry, 36, 9035-9044.  
  9336834 B.E.Jones, P.Rajagopal, and R.E.Klevit (1997).
Phosphorylation on histidine is accompanied by localized structural changes in the phosphocarrier protein, HPr from Bacillus subtilis.
  Protein Sci, 6, 2107-2119.
PDB codes: 1jem 2hid
9201951 J.L.Buchbinder, C.B.Luong, M.F.Browner, and R.J.Fletterick (1997).
Partial activation of muscle phosphorylase by replacement of serine 14 with acidic residues at the site of regulatory phosphorylation.
  Biochemistry, 36, 8039-8044.  
9384566 K.Lin, P.K.Hwang, and R.J.Fletterick (1997).
Distinct phosphorylation signals converge at the catalytic center in glycogen phosphorylases.
  Structure, 5, 1511-1523.  
  8745412 A.M.Dean, A.K.Shiau, and D.E.Koshland (1996).
Determinants of performance in the isocitrate dehydrogenase of Escherichia coli.
  Protein Sci, 5, 341-347.  
8673602 B.L.Stoddard, A.Dean, and P.A.Bash (1996).
Combining Laue diffraction and molecular dynamics to study enzyme intermediates.
  Nat Struct Biol, 3, 590-595.  
8888067 B.L.Stoddard (1996).
Intermediate trapping and laue X-ray diffraction: potential for enzyme mechanism, dynamics, and inhibitor screening.
  Pharmacol Ther, 70, 215-256.  
9000033 J.Stubbe, and L.N.Johnson (1996).
Catalysis and regulation.
  Curr Opin Struct Biol, 6, 733-735.  
8608121 M.J.Brubaker, D.H.Dyer, B.Stoddard, and D.E.Koshland (1996).
Synthesis, kinetics, and structural studies of a photolabile caged isocitrate: a catalytic trigger for isocitrate dehydrogenase.
  Biochemistry, 35, 2854-2864.  
  8745407 R.Chen, J.A.Grobler, J.H.Hurley, and A.M.Dean (1996).
Second-site suppression of regulatory phosphorylation in Escherichia coli isocitrate dehydrogenase.
  Protein Sci, 5, 287-295.
PDB codes: 1gro 1grp
  8580838 K.Pullen, P.Rajagopal, B.R.Branchini, M.E.Huffine, J.Reizer, M.H.Saier, J.M.Scholtz, and R.E.Klevit (1995).
Phosphorylation of serine-46 in HPr, a key regulatory protein in bacteria, results in stabilization of its solution structure.
  Protein Sci, 4, 2478-2486.  
  7730286 N.Almaula, Q.Lu, J.Delgado, S.Belkin, and M.Inouye (1995).
Nucleoside diphosphate kinase from Escherichia coli.
  J Bacteriol, 177, 2524-2529.  
7634071 V.L.Rath, and R.J.Fletterick (1994).
Parallel evolution in two homologues of phosphorylase.
  Nat Struct Biol, 1, 681-690.  
8433976 B.L.Stoddard, and D.E.Koshland (1993).
Molecular recognition analyzed by docking simulations: the aspartate receptor and isocitrate dehydrogenase from Escherichia coli.
  Proc Natl Acad Sci U S A, 90, 1146-1153.  
8381789 D.C.LaPorte (1993).
The isocitrate dehydrogenase phosphorylation cycle: regulation and enzymology.
  J Cell Biochem, 51, 14-18.  
  8514749 S.K.Drake, R.B.Bourret, L.A.Luck, M.I.Simon, and J.J.Falke (1993).
Activation of the phosphosignaling protein CheY. I. Analysis of the phosphorylated conformation by 19F NMR and protein engineering.
  J Biol Chem, 268, 13081-13088.  
1499569 S.M.Shaw, and E.A.Carrey (1992).
Regulation of the mammalian carbamoyl-phosphate synthetase II by effectors and phosphorylation. Altered affinity for ATP and magnesium ions measured using the ammonia-dependent part reaction.
  Eur J Biochem, 207, 957-965.  
1961703 D.Worthylake, N.D.Meadow, S.Roseman, D.I.Liao, O.Herzberg, and S.J.Remington (1991).
Three-dimensional structure of the Escherichia coli phosphocarrier protein IIIglc.
  Proc Natl Acad Sci U S A, 88, 10382-10386.
PDB code: 1f3g
15336195 L.N.Johnson (1991).
Direct interaction or remote control?
  Curr Biol, 1, 17-19.  
2251731 M.H.Saier, L.F.Wu, and J.Reizer (1990).
Regulation of bacterial physiological processes by three types of protein phosphorylating systems.
  Trends Biochem Sci, 15, 391-395.  
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.