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PDBsum entry 1pb3

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Oxidoreductase PDB id
1pb3
Jmol
Contents
Protein chain
416 a.a. *
Ligands
SO4 ×2
GOL ×3
Waters ×284
* Residue conservation analysis
PDB id:
1pb3
Name: Oxidoreductase
Title: Sites of binding and orientation in a four location model fo stereospecificity.
Structure: Isocitrate dehydrogenase [nadp]. Chain: a. Synonym: oxalosuccinate decarboxylase, idh, NADP+-specific engineered: yes. Other_details: wildtype
Source: Escherichia coli. Organism_taxid: 562. Gene: icd or icda or icde or b1136. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
Resolution:
1.70Å     R-factor:   0.194     R-free:   0.216
Authors: A.D.Mesecar,D.E.Koshland Jr.
Key ref: A.D.Mesecar and D.E.Koshland (2000). Sites of binding and orientation in a four-location model for protein stereospecificity. IUBMB Life, 49, 457-466. PubMed id: 10902579 DOI: 10.1080/152165400410326
Date:
14-May-03     Release date:   17-Jun-03    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
Seq:
Struc:
416 a.a.
416 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
Bound ligand (Het Group name = GOL)
matches with 45.45% similarity
+ 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    
 
 
DOI no: 10.1080/152165400410326 IUBMB Life 49:457-466 (2000)
PubMed id: 10902579  
 
 
Sites of binding and orientation in a four-location model for protein stereospecificity.
A.D.Mesecar, D.E.Koshland.
 
  ABSTRACT  
 
The stereospecificity of the enzyme isocitrate dehydrogenase was examined by steady-state kinetics and x-ray crystallography. The enzyme has the intriguing property that the apoenzyme in the absence of divalent metal showed a selectivity for the inactive l-enantiomer of the substrate isocitrate, whereas the enzyme containing magnesium showed selectivity for the physiologically active d-enantiomer. The hydrogen atom on the C2 carbon that is transferred during the reaction was, in both the d- and l-isocitrate complexes, in an orientation very close to that expected for delivery of a hydride ion to the cosubstrate NADP+. The beta-carboxylate that is eliminated as a CO2 molecule during the reaction occupied the same site on the protein in both the d- and l-isocitrate complexes. In addition, the C3 carbon was in the same protein site in both the d- and l-enantiomers. Only the fourth group, the OH atom, was in a very different position in the apo enzyme and in the metal-containing complexes. A four-location model is necessary to explain the enantiomeric specificity of IDH in contrast to the conventional three-point attachment model. The thermodynamic and kinetic ramifications of this model are explored.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20407036 G.C.Bullock, L.L.Delehanty, A.L.Talbot, S.L.Gonias, W.H.Tong, T.A.Rouault, B.Dewar, J.M.Macdonald, J.J.Chruma, and A.N.Goldfarb (2010).
Iron control of erythroid development by a novel aconitase-associated regulatory pathway.
  Blood, 116, 97.  
19672908 J.H.Park, H.J.Ha, W.K.Lee, T.Généreux-Vincent, and R.J.Kazlauskas (2009).
Molecular basis for the stereoselective ammoniolysis of N-alkyl aziridine-2-carboxylates catalyzed by Candida antarctica lipase B.
  Chembiochem, 10, 2213-2222.  
17610893 M.May, S.Mehboob, D.C.Mulhearn, Z.Wang, H.Yu, G.R.Thatcher, B.D.Santarsiero, M.E.Johnson, and A.D.Mesecar (2007).
Structural and functional analysis of two glutamate racemase isozymes from Bacillus anthracis and implications for inhibitor design.
  J Mol Biol, 371, 1219-1237.
PDB codes: 2dwu 2gzm
15736174 V.Sundaresan, and R.Abrol (2005).
Biological chiral recognition: the substrate's perspective.
  Chirality, 17, S30-S39.  
15190582 R.Kafri, and D.Lancet (2004).
Probability rule for chiral recognition.
  Chirality, 16, 369-378.  
12021432 V.Sundaresan, and R.Abrol (2002).
Towards a general model for protein-substrate stereoselectivity.
  Protein Sci, 11, 1330-1339.  
11284679 S.A.Doyle, P.T.Beernink, and D.E.Koshland (2001).
Structural basis for a change in substrate specificity: crystal structure of S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+, and NADP.
  Biochemistry, 40, 4234-4241.
PDB code: 1hj6
11087384 S.A.Doyle, S.Y.Fung, and D.E.Koshland (2000).
Redesigning the substrate specificity of an enzyme: isocitrate dehydrogenase.
  Biochemistry, 39, 14348-14355.  
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.