PDBsum entry 1dqu

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protein links
Lyase PDB id
Protein chain
513 a.a. *
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of the isocitrate lyase from aspergillus n
Structure: Isocitrate lyase. Chain: a. Engineered: yes
Source: Emericella nidulans. Organism_taxid: 162425. Expressed in: emericella nidulans. Expression_system_taxid: 162425. Other_details: multicopy insertion of vector into chromosom
Biol. unit: Tetramer (from PDB file)
2.80Å     R-factor:   0.276     R-free:   0.376
Authors: K.L.Britton,S.J.Langridge,P.J.Baker,K.Weeradechapon,S.E.Sede J.R.De Lucas,D.W.Rice,G.Turner
Key ref:
K.Britton et al. (2000). The crystal structure and active site location of isocitrate lyase from the fungus Aspergillus nidulans. Structure, 8, 349-362. PubMed id: 10801489 DOI: 10.1016/S0969-2126(00)00117-9
05-Jan-00     Release date:   10-May-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P28298  (ACEA_EMENI) -  Isocitrate lyase
538 a.a.
513 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.  - Isocitrate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Glyoxylate Cycle
      Reaction: Isocitrate = succinate + glyoxylate
= succinate
+ glyoxylate
   Enzyme class 3: E.C.  - Methylisocitrate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate = pyruvate + succinate
= pyruvate
+ succinate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   4 terms 
  Biological process     metabolic process   7 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1016/S0969-2126(00)00117-9 Structure 8:349-362 (2000)
PubMed id: 10801489  
The crystal structure and active site location of isocitrate lyase from the fungus Aspergillus nidulans.
K.Britton, S.Langridge, P.J.Baker, K.Weeradechapon, S.E.Sedelnikova, J.R.De Lucas, D.W.Rice, G.Turner.
BACKGROUND: Isocitrate lyase catalyses the first committed step of the carbon-conserving glyoxylate bypass, the Mg(2+)-dependent reversible cleavage of isocitrate into succinate and glyoxylate. This metabolic pathway is an inviting target for the control of a number of diseases, because the enzymes involved in this cycle have been identified in many pathogens including Mycobacterium leprae and Leishmania. RESULTS: As part of a programme of rational drug design the structure of the tetrameric Aspergillus nidulans isocitrate lyase and its complex with glyoxylate and a divalent cation have been solved to 2.8 A resolution using X-ray diffraction. Each subunit comprises two domains, one of which adopts a folding pattern highly reminiscent of the triose phosphate isomerase (TIM) barrel. A 'knot' between subunits observed in the three-dimensional structure, involving residues towards the C terminus, implies that tetramer assembly involves considerable flexibility in this part of the protein. CONCLUSIONS: Difference Fourier analysis together with the pattern of sequence conservation has led to the identification of both the glyoxylate and metal binding sites and implicates the C-terminal end of the TIM barrel as the active site, which is consistent with studies of other enzymes with this fold. Two disordered regions of the polypeptide chain lie close to the active site, one of which includes a critical cysteine residue suggesting that conformational rearrangements are essential for catalysis. Structural similarities between isocitrate lyase and both PEP mutase and enzymes belonging to the enolase superfamily suggest possible relationships in aspects of the mechanism.
  Selected figure(s)  
Figure 6.
Figure 6. Location of the active site in the A. nidulans ICL. (a) A view of the molecular surface of the ICL tetramer, viewed down one of the twofold axes, prepared using the program GRASP [59]. The surface is coloured according to the electrostatic potential (red, negative; blue, positive). The overall surface appears to be fairly neutral with the exception of a highly charged region (red) at the entrance to the TIM barrel where a cluster of conserved negatively charged residues are found. These residues form the divalent cation metal binding site in ICL. (b) The nature of the unexplained difference electron density which lies in the vicinity of the conserved carboxyls (Asp114, Asp168, Asp170 and Glu197). (c) The refined electron-density map at 2.8 showing the location of the divalent metal atom (Mn) and the glyoxylate substrate.
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 349-362) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21332878 M.Nakazawa, M.Nishimura, K.Inoue, M.Ueda, H.Inui, Y.Nakano, and K.Miyatake (2011).
Characterization of a bifunctional glyoxylate cycle enzyme, malate synthase/isocitrate lyase, of Euglena gracilis.
  J Eukaryot Microbiol, 58, 128-133.  
18081320 B.C.Narayanan, W.Niu, Y.Han, J.Zou, P.S.Mariano, D.Dunaway-Mariano, and O.Herzberg (2008).
Structure and function of PA4872 from Pseudomonas aeruginosa, a novel class of oxaloacetate decarboxylase from the PEP mutase/isocitrate lyase superfamily.
  Biochemistry, 47, 167-182.
PDB code: 3b8i
17041184 A.Idnurm, S.S.Giles, J.R.Perfect, and J.Heitman (2007).
Peroxisome function regulates growth on glucose in the basidiomycete fungus Cryptococcus neoformans.
  Eukaryot Cell, 6, 60-72.  
17879748 H.C.Yang, J.Yu, K.B.Oh, D.S.Shin, W.J.Cho, J.Shin, and S.Kim (2007).
Synthesis and evaluation of hydroquinone derivatives as inhibitors of isocitrate lyase.
  Arch Pharm Res, 30, 955-961.  
17244616 Y.Han, H.J.Joosten, W.Niu, Z.Zhao, P.S.Mariano, M.McCalman, J.van Kan, P.J.Schaap, and D.Dunaway-Mariano (2007).
Oxaloacetate hydrolase, the C-C bond lyase of oxalate secreting fungi.
  J Biol Chem, 282, 9581-9590.  
16879647 T.A.Gould, H.van de Langemheen, E.J.Muñoz-Elías, J.D.McKinney, and J.C.Sacchettini (2006).
Dual role of isocitrate lyase 1 in the glyoxylate and methylcitrate cycles in Mycobacterium tuberculosis.
  Mol Microbiol, 61, 940-947.  
15895072 E.J.Muñoz-Elías, and J.D.McKinney (2005).
Mycobacterium tuberculosis isocitrate lyases 1 and 2 are jointly required for in vivo growth and virulence.
  Nat Med, 11, 638-644.  
16151139 M.Brock (2005).
Generation and phenotypic characterization of Aspergillus nidulans methylisocitrate lyase deletion mutants: methylisocitrate inhibits growth and conidiation.
  Appl Environ Microbiol, 71, 5465-5475.  
12842039 B.N.Chaudhuri, M.R.Sawaya, C.Y.Kim, G.S.Waldo, M.S.Park, T.C.Terwilliger, and T.O.Yeates (2003).
The crystal structure of the first enzyme in the pantothenate biosynthetic pathway, ketopantoate hydroxymethyltransferase, from M tuberculosis.
  Structure, 11, 753-764.
PDB code: 1oy0
12837791 F.Schmitzberger, A.G.Smith, C.Abell, and T.L.Blundell (2003).
Comparative analysis of the Escherichia coli ketopantoate hydroxymethyltransferase crystal structure confirms that it is a member of the (betaalpha)8 phosphoenolpyruvate/pyruvate superfamily.
  J Bacteriol, 185, 4163-4171.  
11728873 K.Höner zu Bentrup, and D.G.Russell (2001).
Mycobacterial persistence: adaptation to a changing environment.
  Trends Microbiol, 9, 597-605.  
11526312 K.L.Britton, I.S.Abeysinghe, P.J.Baker, V.Barynin, P.Diehl, S.J.Langridge, B.A.McFadden, S.E.Sedelnikova, T.J.Stillman, K.Weeradechapon, and D.W.Rice (2001).
The structure and domain organization of Escherichia coli isocitrate lyase.
  Acta Crystallogr D Biol Crystallogr, 57, 1209-1218.
PDB code: 1igw
11422389 M.Brock, D.Darley, S.Textor, and W.Buckel (2001).
2-Methylisocitrate lyases from the bacterium Escherichia coli and the filamentous fungus Aspergillus nidulans: characterization and comparison of both enzymes.
  Eur J Biochem, 268, 3577-3586.  
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.