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PDBsum entry 1a05
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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1a05

 

 

 

 

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Contents
Protein chains
357 a.a. *
Ligands
IPM ×2
Metals
_MG ×2
Waters ×504
* Residue conservation analysis
PDB id:
1a05
Name: Oxidoreductase
Title: Crystal structure of the complex of 3-isopropylmalate dehydrogenase from thiobacillus ferrooxidans with 3-isopropylmalate
Structure: 3-isopropylmalate dehydrogenase. Chain: a, b. Synonym: ipmdh, imdh. Engineered: yes
Source: Acidithiobacillus ferrooxidans. Organism_taxid: 920. Strain: ap19-3. Gene: leub. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.00Å     R-factor:   0.198     R-free:   0.275
Authors: K.Imada,K.Inagaki,H.Matsunami,H.Kawaguchi,H.Tanaka,N.Tanaka,K.Namba
Key ref:
K.Imada et al. (1998). Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism. Structure, 6, 971-982. PubMed id: 9739088 DOI: 10.1016/S0969-2126(98)00099-9
Date:
09-Dec-97     Release date:   17-Jun-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q56268  (LEU3_ACIFR) -  3-isopropylmalate dehydrogenase from Acidithiobacillus ferrooxidans
Seq:
Struc: 		358 a.a.
357 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.85  - 3-isopropylmalate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Leucine Biosynthesis
      Reaction: (2R,3S)-3-isopropylmalate + NAD+ = 4-methyl-2-oxopentanoate + CO2 + NADH
(2R,3S)-3-isopropylmalate
Bound ligand (Het Group name = IPM)
corresponds exactly 		+ NAD(+)
 = 4-methyl-2-oxopentanoate
 + CO2
 + NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(98)00099-9 Structure 6:971-982 (1998)
PubMed id: 9739088  
 
 
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.
K.Imada, K.Inagaki, H.Matsunami, H.Kawaguchi, H.Tanaka, N.Tanaka, K.Namba.
 
  ABSTRACT  
 
BACKGROUND: 3-Isopropylmalate dehydrogenase (IPMDH) and isocitrate dehydrogenase (ICDH) belong to a unique family of bifunctional decarboxylating dehydrogenases. Although the ICDH dimer catalyzes its reaction under a closed conformation, known structures of the IPMDH dimer (without substrate) adopt a fully open or a partially closed form. Considering the similarity in the catalytic mechanism, the IPMDH dimer must be in a fully closed conformation during the reaction. A large conformational change should therefore occur upon substrate binding. RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method. The structure shows a fully closed conformation and the substrate-binding site is quite similar to that of ICDH except for a region around the gamma-isopropyl group. The gamma group is recognized by a unique hydrophobic pocket, which includes Glu88, Leu91 and Leu92 from subunit 1 and Val193' from subunit 2. CONCLUSIONS: A large movement of domain 1 is induced by substrate binding, which results in the formation of the hydrophobic pocket for the gamma-isopropyl moiety of IPM. A glutamic acid in domain 1, Glu88, participates in the formation of the hydrophobic pocket. The C beta and C gamma atoms of Glu88 interact with the gamma-isopropyl moiety of IPM and are central to the recognition of substrate. The acidic tip of Glu88 is likely to interact with the nicotinamide mononucleotide (NMN) ribose of NAD+ in the ternary complex. This structure clearly explains the substrate specificity of IPMDH.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Comparison of the g moiety recognition site. (a) A space-filling stereo drawing of the active site of Tf-IPMDH, viewed from the right-hand side of Figure 7b. The substrate is shown in ball-and-stick representation. Atoms are color-coded: oxygen, red; nitrogen, blue; and carbon, gray. A green ball represents a sulfur atom of a methionine residue and a small magenta ball indicates the magnesium ion. The carbon atoms in the hydrophobic pocket are highlighted in orange. Residues forming the hydrophobic pocket are labeled with their residue numbers. Schematic representations of the active site of (b) Tf-IPMDH (closed conformation), (c) Ec-ICDH (closed conformation), (d) St-IPMDH (closed conformation), (e) Tt-IPMDH IPM complex (open conformation). The orientation is as in (a). (d) Was generated by the superposition of IPM and Mg of the Tf-IPMDH binary complex onto the structure of St-IPMDH solved without IPM and Mg. The protein backbone is shown in a ribbon representation. The substrate molecules and sidechains lying in the active sites are shown in ball-and-stick representation. The color coding of the atoms is as in (a). Residues interacting with the g moiety of the substrates are labeled with their residue numbers. The figures were generated with MOLSCRIPT [36] and RASTER3D [37].
 
  The above figure is reprinted by permission from Cell Press: Structure (1998, 6, 971-982) copyright 1998.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22349232 T.Nagae, T.Kawamura, L.M.Chavas, K.Niwa, M.Hasegawa, C.Kato, and N.Watanabe (2012).
High-pressure-induced water penetration into 3-isopropylmalate dehydrogenase.
  Acta Crystallogr D Biol Crystallogr, 68, 300-309.
PDB codes: 3vkz 3vl2 3vl3 3vl4 3vl6 3vl7
21387033 Ã.‰.Gráczer, A.Merli, R.K.Singh, M.Karuppasamy, P.Závodszky, M.S.Weiss, and M.Vas (2011).
Atomic level description of the domain closure in a dimeric enzyme: thermus thermophilus 3-isopropylmalate dehydrogenase.
  Mol Biosyst, 7, 1646-1659.
PDB codes: 2y3z 2y40 2y41 2y42
20975933 M.Lunzer, G.B.Golding, and A.M.Dean (2010).
Pervasive cryptic epistasis in molecular evolution.
  PLoS Genet, 6, e1001162.  
20072606 M.Röttig, C.Rausch, and O.Kohlbacher (2010).
Combining structure and sequence information allows automated prediction of substrate specificities within enzyme families.
  PLoS Comput Biol, 6, e1000636.  
19527660 I.Hajdú, A.Szilágyi, J.Kardos, and P.Závodszky (2009).
A link between hinge-bending domain motions and the temperature dependence of catalysis in 3-isopropylmalate dehydrogenase.
  Biophys J, 96, 5003-5012.  
19331660 J.R.Weber (2009).
ProteinShader: illustrative rendering of macromolecules.
  BMC Struct Biol, 9, 19.  
19897891 R.Kasahara, T.Sato, H.Tamegai, and C.Kato (2009).
Piezo-adapted 3-isopropylmalate dehydrogenase of the obligate piezophile Shewanella benthica DB21MT-2 isolated from the 11,000-m depth of the Mariana Trench.
  Biosci Biotechnol Biochem, 73, 2541-2543.  
17634983 K.Imada, T.Tamura, R.Takenaka, I.Kobayashi, K.Namba, and K.Inagaki (2008).
Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity.
  Proteins, 70, 63-71.
PDB code: 2d4v
18854331 M.Sasaki, M.Uno, S.Akanuma, and A.Yamagishi (2008).
Random mutagenesis improves the low-temperature activity of the tetrameric 3-isopropylmalate dehydrogenase from the hyperthermophile Sulfolobus tokodaii.
  Protein Eng Des Sel, 21, 721-727.  
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.  
16699828 J.A.McCourt, and R.G.Duggleby (2006).
Acetohydroxyacid synthase and its role in the biosynthetic pathway for branched-chain amino acids.
  Amino Acids, 31, 173-210.  
16767773 O.V.Kalinina, and M.S.Gelfand (2006).
Amino acid residues that determine functional specificity of NADP- and NAD-dependent isocitrate and isopropylmalate dehydrogenases.
  Proteins, 64, 1001-1009.  
16088877 H.Turakainen, and M.Korhola (2005).
Cloning, sequencing and application of the LEU2 gene from the sour dough yeast Candida milleri.
  Yeast, 22, 805-812.  
16166541 J.Miyazaki, K.Asada, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (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.
PDB code: 1x0l
15103616 F.Dupuis, J.F.Sadoc, and J.P.Mornon (2004).
Protein secondary structure assignment through Voronoï tessellation.
  Proteins, 55, 519-528.  
12427751 J.Miyazaki, N.Kobashi, M.Nishiyama, and H.Yamane (2003).
Characterization of homoisocitrate dehydrogenase involved in lysine biosynthesis of an extremely thermophilic bacterium, Thermus thermophilus HB27, and evolutionary implication of beta-decarboxylating dehydrogenase.
  J Biol Chem, 278, 1864-1871.  
12896974 J.Sivaraman, Y.Li, J.Banks, D.E.Cane, A.Matte, and M.Cygler (2003).
Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway.
  J Biol Chem, 278, 43682-43690.
PDB codes: 1ps6 1ps7 1ptm
12855708 Y.Yasutake, S.Watanabe, M.Yao, Y.Takada, N.Fukunaga, and I.Tanaka (2003).
Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution.
  J Biol Chem, 278, 36897-36904.
PDB code: 1j1w
12204383 H.Inoue, T.Tamura, N.Ehara, A.Nishito, Y.Nakayama, M.Maekawa, K.Imada, H.Tanaka, and K.Inagaki (2002).
Biochemical and molecular characterization of the NAD(+)-dependent isocitrate dehydrogenase from the chemolithotroph Acidithiobacillus thiooxidans.
  FEMS Microbiol Lett, 214, 127-132.  
12454487 M.Karlström, I.H.Steen, G.Tibbelin, T.Lien, N.K.Birkeland, and R.Ladenstein (2002).
Crystallization and preliminary X-ray structure analysis of isocitrate dehydrogenase from two hyperthermophiles, Aeropyrum pernix and Thermotoga maritima.
  Acta Crystallogr D Biol Crystallogr, 58, 2162-2164.  
11826966 M.Fujita, H.Tamegai, T.Eguchi, and K.Kakinuma (2001).
Novel substrate specificity of designer 3-isopropylmalate dehydrogenase derived from Thermus thermophilus HB8.
  Biosci Biotechnol Biochem, 65, 2695-2700.  
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
  16232891 H.Kawaguchi, K.Inagaki, H.Matsunami, Y.Nakayama, T.Tano, and H.Tanaka (2000).
Purification and characterization of 3-isopropylmalate dehydrogenase from Thiobacillus thiooxidans.
  J Biosci Bioeng, 90, 459-461.  
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.

 

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