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Lyase(carbon-oxygen) PDB id
8acn
Jmol
Contents
Protein chain
753 a.a. *
Ligands
SF4-NIC
Waters ×321
* Residue conservation analysis
PDB id:
8acn
Name: Lyase(carbon-oxygen)
Title: Crystal structures of aconitase with isocitrate and nitroisocitrate bound
Structure: Aconitase. Chain: a. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913
Resolution:
2.00Å     R-factor:   0.161    
Authors: H.Lauble,M.C.Kennedy,H.Beinert,C.D.Stout
Key ref:
H.Lauble et al. (1992). Crystal structures of aconitase with isocitrate and nitroisocitrate bound. Biochemistry, 31, 2735-2748. PubMed id: 1547214 DOI: 10.1021/bi00125a014
Date:
15-May-91     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20004  (ACON_BOVIN) -  Aconitate hydratase, mitochondrial
Seq:
Struc: 		 
Seq:
Struc: 		780 a.a.
753 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.3  - Aconitate hydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Aconitate Hydratase
      Reaction: Citrate = isocitrate
Citrate
 =
isocitrate
Bound ligand (Het Group name = NIC)
matches with 62.00% similarity
      Cofactor: Iron-sulfur
Iron-sulfur
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   1 term 
  Biological process     metabolic process   3 terms 
  Biochemical function     lyase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi00125a014 Biochemistry 31:2735-2748 (1992)
PubMed id: 1547214  
 
 
Crystal structures of aconitase with isocitrate and nitroisocitrate bound.
H.Lauble, M.C.Kennedy, H.Beinert, C.D.Stout.
 
  ABSTRACT  
 
The crystal structures of mitochondrial aconitase with isocitrate and nitroisocitrate bound have been solved and refined to R factors of 0.179 and 0.161, respectively, for all observed data in the range 8.0-2.1 A. Porcine heart enzyme was used for determining the structure with isocitrate bound. The presence of isocitrate in the crystals was corroborated by Mössbauer spectroscopy. Bovine heart enzyme was used for determining the structure with the reaction intermediate analogue nitroisocitrate bound. The inhibitor binds to the enzyme in a manner virtually identical to that of isocitrate. Both compounds bind to the unique Fe atom of the [4Fe-4S] cluster via a hydroxyl oxygen and one carboxyl oxygen. A H2O molecule is also bound, making Fe six-coordinate. The unique Fe is pulled away approximately 0.2 A from the corner of the cubane compared to the position it would occupy in a symmetrically ligated [4Fe-4S] cluster. At least 23 residues from all four domains of aconitase contribute to the active site. These residues participate in substrate recognition (Arg447, Arg452, Arg580, Arg644, Gln72, Ser166, Ser643), cluster ligation and interaction (Cys358, Cys421, Cys424, Asn258, Asn446), and hydrogen bonds supporting active site side chains (Ala74, Asp568, Ser571, Thr567). Residues implicated in catalysis are Ser642 and three histidine-carboxylate pairs (Asp100-His101, Asp165-His147, Glu262-His167). The base necessary for proton abstraction from C beta of isocitrate appears to be Ser642; the O gamma atom is proximal to the calculated hydrogen position, while the environment of O gamma suggests stabilization of an alkoxide (an oxyanion hole formed by the amide and side chain of Arg644). The histidine-carboxylate pairs appear to be required for proton transfer reactions involving two oxygens bound to Fe, one derived from solvent (bound H2O) and one derived from substrate hydroxyl. Each oxygen is in contact with a histidine, and both are in contact with the side chain of Asp165, which bridges the two sites on the six-coordinate Fe.
 

Literature references that cite this PDB file's key reference

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PDB code: 1l5j
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The iron-responsive element-binding protein: localization of the RNA-binding site to the aconitase active-site cleft.
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The major iron-containing protein of Legionella pneumophila is an aconitase homologous with the human iron-responsive element-binding protein.
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Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster.
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1281544 D.J.Haile, T.A.Rouault, J.B.Harford, M.C.Kennedy, G.A.Blondin, H.Beinert, and R.D.Klausner (1992).
Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding.
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Protein metal-binding sites.
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Purification and characterization of cytosolic aconitase from beef liver and its relationship to the iron-responsive element binding protein.
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An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein.
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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.