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PDBsum entry 1x0l

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protein Protein-protein interface(s) links
Oxidoreductase PDB id
1x0l
Jmol PyMol
Contents
Protein chains
333 a.a. *
Waters ×378
* Residue conservation analysis
PDB id:
1x0l
Name: Oxidoreductase
Title: Crystal structure of tetrameric homoisocitrate dehydrogenase extreme thermophile, thermus thermophilus
Structure: Homoisocitrate dehydrogenase. Chain: a, b. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274. Gene: hicdh. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.85Å     R-factor:   0.216     R-free:   0.248
Authors: J.Miyazaki,K.Asada,S.Fushinobu,T.Kuzuyama,M.Nishiyama
Key ref: J.Miyazaki et al. (2005). Crystal structure of tetrameric homoisocitrate dehydrogenase from an extreme thermophile, Thermus thermophilus: involvement of hydrophobic dimer-dimer interaction in extremely high thermotolerance. J Bacteriol, 187, 6779-6788. PubMed id: 16166541
Date:
24-Mar-05     Release date:   04-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q72IW9  (Q72IW9_THET2) -  Homoisocitrate dehydrogenase
Seq:
Struc:
334 a.a.
333 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.87  - Homoisocitrate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH
(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate
+ NAD(+)
= 2-oxoadipate
+ CO(2)
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
J Bacteriol 187:6779-6788 (2005)
PubMed id: 16166541  
 
 
Crystal structure of tetrameric homoisocitrate dehydrogenase from an extreme thermophile, Thermus thermophilus: involvement of hydrophobic dimer-dimer interaction in extremely high thermotolerance.
J.Miyazaki, K.Asada, S.Fushinobu, T.Kuzuyama, M.Nishiyama.
 
  ABSTRACT  
 
The crystal structure of homoisocitrate dehydrogenase involved in lysine biosynthesis from Thermus thermophilus (TtHICDH) was determined at 1.85-A resolution. Arg85, which was shown to be a determinant for substrate specificity in our previous study, is positioned close to the putative substrate binding site and interacts with Glu122. Glu122 is highly conserved in the equivalent position in the primary sequence of ICDH and archaeal 3-isopropylmalate dehydrogenase (IPMDH) but interacts with main- and side-chain atoms in the same domain in those paralogs. In addition, a conserved Tyr residue (Tyr125 in TtHICDH) which extends its side chain toward a substrate and thus has a catalytic function in the related beta-decarboxylating dehydrogenases, is flipped out of the substrate-binding site. These results suggest the possibility that the conformation of the region containing Glu122-Tyr125 is changed upon substrate binding in TtHICDH. The crystal structure of TtHICDH also reveals that the arm region is involved in tetramer formation via hydrophobic interactions and might be responsible for the high thermotolerance. Mutation of Val135, located in the dimer-dimer interface and involved in the hydrophobic interaction, to Met alters the enzyme to a dimer (probably due to steric perturbation) and markedly decreases the thermal inactivation temperature. Both the crystal structure and the mutation analysis indicate that tetramer formation is involved in the extremely high thermotolerance of TtHICDH.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20516620 R.Malik, and R.E.Viola (2010).
Structural characterization of tartrate dehydrogenase: a versatile enzyme catalyzing multiple reactions.
  Acta Crystallogr D Biol Crystallogr, 66, 673-684.
PDB codes: 3flk 3fmx
19490113 A.Yoshida, T.Tomita, H.Kono, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (2009).
Crystal structures of the regulatory subunit of Thr-sensitive aspartate kinase from Thermus thermophilus.
  FEBS J, 276, 3124-3136.
PDB codes: 2dt9 2zho
19530703 Y.Lin, A.H.West, and P.F.Cook (2009).
Site-directed mutagenesis as a probe of the acid-base catalytic mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae.
  Biochemistry, 48, 7305-7312.  
18256028 A.B.Taylor, G.Hu, P.J.Hart, and L.McAlister-Henn (2008).
Allosteric motions in structures of yeast NAD+-specific isocitrate dehydrogenase.
  J Biol Chem, 283, 10872-10880.
PDB codes: 3blv 3blw 3blx
18203822 M.Aoshima, and Y.Igarashi (2008).
Nondecarboxylating and decarboxylating isocitrate dehydrogenases: oxalosuccinate reductase as an ancestral form of isocitrate dehydrogenase.
  J Bacteriol, 190, 2050-2055.  
17160675 R.Stokke, D.Madern, A.E.Fedøy, S.Karlsen, N.K.Birkeland, and I.H.Steen (2007).
Biochemical characterization of isocitrate dehydrogenase from Methylococcus capsulatus reveals a unique NAD+-dependent homotetrameric enzyme.
  Arch Microbiol, 187, 361-370.  
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.

 

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