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PDBsum entry 1hyg

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1hyg
Jmol
Contents
Protein chains
313 a.a. *
Ligands
NAP ×2
Waters ×140
* Residue conservation analysis
PDB id:
1hyg
Name: Oxidoreductase
Title: Crystal structure of mj0490 gene product, the family of lactate/malate dehydrogenase
Structure: L-lactate/malate dehydrogenase. Chain: a, b. Engineered: yes
Source: Methanocaldococcus jannaschii. Organism_taxid: 2190. Gene: mj0490. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.216     R-free:   0.282
Authors: B.I.Lee,C.Chang,S.-J.Cho,S.W.Suh
Key ref:
B.I.Lee et al. (2001). Crystal structure of the MJ0490 gene product of the hyperthermophilic archaebacterium Methanococcus jannaschii, a novel member of the lactate/malate family of dehydrogenases. J Mol Biol, 307, 1351-1362. PubMed id: 11292347 DOI: 10.1006/jmbi.2001.4532
Date:
19-Jan-01     Release date:   25-Apr-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q60176  (MDH_METJA) -  Malate dehydrogenase
Seq:
Struc:
313 a.a.
313 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.1.1.1.37  - Malate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Citric acid cycle
      Reaction: (S)-malate + NAD+ = oxaloacetate + NADH
(S)-malate
+
NAD(+)
Bound ligand (Het Group name = NAP)
matches with 91.00% similarity
= oxaloacetate
+ NADH
   Enzyme class 2: E.C.1.1.1.82  - Malate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-malate + NADP+ = oxaloacetate + NADPH
(S)-malate
+
NADP(+)
Bound ligand (Het Group name = NAP)
corresponds exactly
= oxaloacetate
+ NADPH
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   1 term 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.2001.4532 J Mol Biol 307:1351-1362 (2001)
PubMed id: 11292347  
 
 
Crystal structure of the MJ0490 gene product of the hyperthermophilic archaebacterium Methanococcus jannaschii, a novel member of the lactate/malate family of dehydrogenases.
B.I.Lee, C.Chang, S.J.Cho, S.H.Eom, K.K.Kim, Y.G.Yu, S.W.Suh.
 
  ABSTRACT  
 
The MJ0490 gene, one of the only two genes of Methanococcus jannaschii showing sequence similarity to the lactate/malate family of dehydrogenases, was classified initially as coding for a putative l-lactate dehydrogenase (LDH). It has been re-classified as a malate dehydrogenase (MDH) gene, because it shows significant sequence similarity to MT0188, MDH II from Methanobacterium thermoautotrophicum strain DeltaH. The three-dimensional structure of its gene product has been determined in two crystal forms: a "dimeric" structure in the orthorhombic crystal at 1.9 A resolution and a "tetrameric" structure in the tetragonal crystal at 2.8 A. These structures share a similar subunit fold with other LDHs and MDHs. The tetrameric structure resembles typical tetrameric LDHs. The dimeric structure is equivalent to the P-dimer of tetrameric LDHs, unlike dimeric MDHs, which correspond to the Q-dimer. The structure reveals that the cofactor NADP(H) is bound at the active site, despite the fact that it was not intentionally added during protein purification and crystallization. The preference of NADP(H) over NAD(H) has been supported by activity assays. The cofactor preference is explained by the presence of a glycine residue in the cofactor binding pocket (Gly33), which replaces a conserved aspartate (or glutamate) residue in other NAD-dependent LDHs or MDHs. Preference for NADP(H) is contributed by hydrogen bonds between the oxygen atoms of the monophosphate group and the ribose sugar of adenosine in NADP(H) and the side-chains of Ser9, Arg34, His36, and Ser37. The MDH activity of MJ0490 is made possible by Arg86, which is conserved in MDHs but not in LDHs. The enzymatic assay showed that the MJ0490 protein possesses the fructose-1,6-bisphosphate-activated LDH activity (reduction). Thus the MJ0490 gene product appears to be a novel member of the lactate/malate dehydrogenase family, displaying an LDH scaffold and exhibiting a relaxed substrate and cofactor specificities in NADP(H) and NAD(H)-dependent malate and lactate dehydrogenase reactions.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Overall structure of MJ0490 protein. (a) Stereo ribbon diagram of the subunit model, and stereo C^a tracings of (b) terameric structure and (c) dimeric structure. NADP+ molecules are shown in orange (in (a)) or in blue (in (b), and (c)). These Figures were drawn by MOLSCRIPT [Kraulis 1991] and Raster3D [Merritt and Murphy 1994].
Figure 3.
Figure 3. (a) Stereo view of the final (2F[o] - F[c]) electron density map around the bound NADP+, calculated using 20.0-1.9 Å data and contoured at 1.0s. (b) Stereo view of the cofactor binding site. The NADP+ molecule is in dark olive green and interacting residues are drawn in orange. Broken lines indicate hydrogen bonds or close contacts.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 307, 1351-1362) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17487443 L.J.Yennaco, Y.Hu, and J.F.Holden (2007).
Characterization of malate dehydrogenase from the hyperthermophilic archaeon Pyrobaculum islandicum.
  Extremophiles, 11, 741-746.  
  18007057 T.Fujii, T.Oikawa, I.Muraoka, K.Soda, and Y.Hata (2007).
Crystallization and preliminary X-ray diffraction studies of tetrameric malate dehydrogenase from the novel Antarctic psychrophile Flavobacterium frigidimaris KUC-1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 983-986.  
16479375 G.Yang, C.Jing, P.Zhu, X.Hu, J.Xu, Z.Wu, and X.Yu (2006).
Molecular cloning and characterization of a novel lactate dehydrogenase gene from Clonorchis sinensis.
  Parasitol Res, 99, 55-64.  
16585745 L.L.Grochowski, H.Xu, and R.H.White (2006).
Identification of lactaldehyde dehydrogenase in Methanocaldococcus jannaschii and its involvement in production of lactate for F420 biosynthesis.
  J Bacteriol, 188, 2836-2844.  
16868745 M.Tehei, R.Daniel, and G.Zaccai (2006).
Fundamental and biotechnological applications of neutron scattering measurements for macromolecular dynamics.
  Eur Biophys J, 35, 551-558.  
16203729 M.Tehei, D.Madern, B.Franzetti, and G.Zaccai (2005).
Neutron scattering reveals the dynamic basis of protein adaptation to extreme temperature.
  J Biol Chem, 280, 40974-40979.  
15598351 S.Cheek, Y.Qi, S.S.Krishna, L.N.Kinch, and N.V.Grishin (2004).
4SCOPmap: automated assignment of protein structures to evolutionary superfamilies.
  BMC Bioinformatics, 5, 197.  
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
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.