PDBsum entry 1d3a

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
303 a.a. *
_CL ×2
Waters ×32
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of the wild type halophilic malate dehydro the apo form
Structure: Halophilic malate dehydrogenase. Chain: a, b. Engineered: yes
Source: Haloarcula marismortui. Organism_taxid: 2238. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.94Å     R-factor:   0.202     R-free:   0.244
Authors: S.B.Richard,D.Madern,E.Garcin,G.Zaccai
Key ref:
S.B.Richard et al. (2000). Halophilic adaptation: novel solvent protein interactions observed in the 2.9 and 2.6 A resolution structures of the wild type and a mutant of malate dehydrogenase from Haloarcula marismortui. Biochemistry, 39, 992. PubMed id: 10653643 DOI: 10.1021/bi991001a
28-Sep-99     Release date:   20-Mar-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q07841  (MDH_HALMA) -  Malate dehydrogenase
304 a.a.
303 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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

Citric acid cycle
      Reaction: (S)-malate + NAD+ = oxaloacetate + NADH
+ NAD(+)
= oxaloacetate
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     4 terms  


DOI no: 10.1021/bi991001a Biochemistry 39:992 (2000)
PubMed id: 10653643  
Halophilic adaptation: novel solvent protein interactions observed in the 2.9 and 2.6 A resolution structures of the wild type and a mutant of malate dehydrogenase from Haloarcula marismortui.
S.B.Richard, D.Madern, E.Garcin, G.Zaccai.
Previous biophysical studies of tetrameric malate dehydrogenase from the halophilic archaeon Haloarcula marismortui (Hm MalDH) have revealed the importance of protein-solvent interactions for its adaptation to molar salt conditions that strongly affect protein solubility, stability, and activity, in general. The structures of the E267R stability mutant of apo (-NADH) Hm MalDH determined to 2.6 A resolution and of apo (-NADH) wild type Hm MalDH determined to 2.9 A resolution, presented here, highlight a variety of novel protein-solvent features involved in halophilic adaptation. The tetramer appears to be stabilized by ordered water molecule networks and intersubunit complex salt bridges "locked" in by bound solvent chloride and sodium ions. The E267R mutation points into a central ordered water cavity, disrupting protein-solvent interactions. The analysis of the crystal structures showed that halophilic adaptation is not aimed uniquely at "protecting" the enzyme from the extreme salt conditions, as may have been expected, but, on the contrary, consists of mechanisms that harness the high ionic concentration in the environment.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20845078 Z.D.Wang, B.J.Wang, Y.D.Ge, W.Pan, J.Wang, L.Xu, A.M.Liu, and G.P.Zhu (2011).
Expression and identification of a thermostable malate dehydrogenase from multicellular prokaryote Streptomyces avermitilis MA-4680.
  Mol Biol Rep, 38, 1629-1636.  
20000704 M.Toth, C.Smith, H.Frase, S.Mobashery, and S.Vakulenko (2010).
An antibiotic-resistance enzyme from a deep-sea bacterium.
  J Am Chem Soc, 132, 816-823.
PDB code: 3lez
21071865 Y.D.Ge, Z.Y.Cao, Z.D.Wang, L.L.Chen, Y.M.Zhu, and G.P.Zhu (2010).
Identification and Biochemical Characterization of a Thermostable Malate Dehydrogenase from the Mesophile Streptomyces coelicolor A3(2).
  Biosci Biotechnol Biochem, 74, 2194-2201.  
19184366 A.Pradhan, P.Mukherjee, A.K.Tripathi, M.A.Avery, L.A.Walker, and B.L.Tekwani (2009).
Analysis of quaternary structure of a [LDH-like] malate dehydrogenase of Plasmodium falciparum with oligomeric mutants.
  Mol Cell Biochem, 325, 141-148.  
19698123 J.A.Winter, P.Christofi, S.Morroll, and K.A.Bunting (2009).
The crystal structure of Haloferax volcanii proliferating cell nuclear antigen reveals unique surface charge characteristics due to halophilic adaptation.
  BMC Struct Biol, 9, 55.
PDB code: 3ifv
19525351 L.Malki, M.Yanku, I.Borovok, G.Cohen, M.Mevarech, and Y.Aharonowitz (2009).
Identification and characterization of gshA, a gene encoding the glutamate-cysteine ligase in the halophilic archaeon Haloferax volcanii.
  J Bacteriol, 191, 5196-5204.  
20016684 X.Tadeo, B.López-Méndez, T.Trigueros, A.Laín, D.Castaño, and O.Millet (2009).
Structural basis for the aminoacid composition of proteins from halophilic archea.
  PLoS Biol, 7, e1000257.
PDB code: 2kac
18312415 L.Niiranen, B.Altermark, B.O.Brandsdal, H.K.Leiros, R.Helland, A.O.Smalås, and N.P.Willassen (2008).
Effects of salt on the kinetics and thermodynamic stability of endonuclease I from Vibrio salmonicida and Vibrio cholerae.
  FEBS J, 275, 1593-1605.
PDB code: 2vnd
18397532 S.Paul, S.K.Bag, S.Das, E.T.Harvill, and C.Dutta (2008).
Molecular signature of hypersaline adaptation: insights from genome and proteome composition of halophilic prokaryotes.
  Genome Biol, 9, R70.  
18189118 Y.Cao, L.Liao, X.W.Xu, A.Oren, C.Wang, X.F.Zhu, and M.Wu (2008).
Characterization of alcohol dehydrogenase from the haloalkaliphilic archaeon Natronomonas pharaonis.
  Extremophiles, 12, 471-476.  
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.  
17215355 M.Tehei, B.Franzetti, K.Wood, F.Gabel, E.Fabiani, M.Jasnin, M.Zamponi, D.Oesterhelt, G.Zaccai, M.Ginzburg, and B.Z.Ginzburg (2007).
Neutron scattering reveals extremely slow cell water in a Dead Sea organism.
  Proc Natl Acad Sci U S A, 104, 766-771.  
15894606 L.Premkumar, H.M.Greenblatt, U.K.Bageshwar, T.Savchenko, I.Gokhman, J.L.Sussman, and A.Zamir (2005).
Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog.
  Proc Natl Acad Sci U S A, 102, 7493-7498.
PDB code: 1y7w
15979821 T.Bhatnagar, S.Boutaiba, H.Hacene, J.L.Cayol, M.L.Fardeau, B.Ollivier, and J.C.Baratti (2005).
Lipolytic activity from Halobacteria: screening and hydrolase production.
  FEMS Microbiol Lett, 248, 133-140.  
15014443 A.Irimia, D.Madern, G.Zaccaï, and F.M.Vellieux (2004).
Methanoarchaeal sulfolactate dehydrogenase: prototype of a new family of NADH-dependent enzymes.
  EMBO J, 23, 1234-1244.
PDB codes: 1rfm 2x06
15221656 D.Madern, M.Camacho, A.Rodríguez-Arnedo, M.J.Bonete, and G.Zaccai (2004).
Salt-dependent studies of NADP-dependent isocitrate dehydrogenase from the halophilic archaeon Haloferax volcanii.
  Extremophiles, 8, 377-384.  
12471605 A.Paiardini, G.Gianese, F.Bossa, and S.Pascarella (2003).
Structural plasticity of thermophilic serine hydroxymethyltransferases.
  Proteins, 50, 122-134.  
12595728 P.Chantawannakul, K.Yoshimune, Y.Shirakihara, A.Shiratori, M.Wakayama, and M.Moriguchi (2003).
Crystallization and preliminary X-ray crystallographic studies of salt-tolerant glutaminase from Micrococcus luteus K-3.
  Acta Crystallogr D Biol Crystallogr, 59, 566-568.  
  15803659 B.Franzetti, G.Schoehn, D.Garcia, R.W.Ruigrok, and G.Zaccai (2002).
Characterization of the proteasome from the extremely halophilic archaeon Haloarcula marismortui.
  Archaea, 1, 53-61.  
11170454 A.K.Bandyopadhyay, G.Krishnamoorthy, and H.M.Sonawat (2001).
Structural stabilization of [2Fe-2S] ferredoxin from Halobacterium salinarum.
  Biochemistry, 40, 1284-1292.  
11566761 A.Solovyova, P.Schuck, L.Costenaro, and C.Ebel (2001).
Non-ideality by sedimentation velocity of halophilic malate dehydrogenase in complex solvents.
  Biophys J, 81, 1868-1880.  
11418554 H.Ichiki, Y.Tanaka, K.Mochizuki, K.Yoshimatsu, T.Sakurai, and T.Fujiwara (2001).
Purification, characterization, and genetic analysis of Cu-containing dissimilatory nitrite reductase from a denitrifying halophilic archaeon, Haloarcula marismortui.
  J Bacteriol, 183, 4149-4156.  
11734642 M.Tehei, D.Madern, C.Pfister, and G.Zaccai (2001).
Fast dynamics of halophilic malate dehydrogenase and BSA measured by neutron scattering under various solvent conditions influencing protein stability.
  Proc Natl Acad Sci U S A, 98, 14356-14361.  
10998181 D.Madern (2000).
The putative L-lactate dehydrogenase from Methanococcus jannaschii is an NADPH-dependent L-malate dehydrogenase.
  Mol Microbiol, 37, 1515-1520.  
11026680 M.Mevarech, F.Frolow, and L.M.Gloss (2000).
Halophilic enzymes: proteins with a grain of salt.
  Biophys Chem, 86, 155-164.  
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 code is shown on the right.