PDBsum entry 1mld

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Oxidoreductase(NAD(a)-choh(d)) PDB id
Protein chains
313 a.a. *
CIT ×4
Waters ×521
* Residue conservation analysis
PDB id:
Name: Oxidoreductase(NAD(a)-choh(d))
Title: Refined structure of mitochondrial malate dehydrogenase from porcine heart and the consensus structure for dicarboxylic acid oxidoreductases
Structure: Malate dehydrogenase. Chain: a, b, c, d. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823
Biol. unit: Dimer (from PQS)
1.83Å     R-factor:   0.211    
Authors: W.B.Gleason,Z.Fu,J.J.Birktoft,L.J.Banaszak
Key ref:
W.B.Gleason et al. (1994). Refined crystal structure of mitochondrial malate dehydrogenase from porcine heart and the consensus structure for dicarboxylic acid oxidoreductases. Biochemistry, 33, 2078-2088. PubMed id: 8117664 DOI: 10.1021/bi00174a014
24-Jan-94     Release date:   26-Jan-95    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00346  (MDHM_PIG) -  Malate dehydrogenase, mitochondrial
338 a.a.
313 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
Bound ligand (Het Group name = CIT)
matches with 69.00% similarity
+ NAD(+)
= oxaloacetate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     oxidation-reduction process   6 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1021/bi00174a014 Biochemistry 33:2078-2088 (1994)
PubMed id: 8117664  
Refined crystal structure of mitochondrial malate dehydrogenase from porcine heart and the consensus structure for dicarboxylic acid oxidoreductases.
W.B.Gleason, Z.Fu, J.Birktoft, L.Banaszak.
The crystal structure of mitochondrial malate dehydrogenase from porcine heart contains four identical subunits in the asymmetric unit of a monoclinic cell. Although the molecule functions as a dimer in solution, it exists as a tetramer with 222 point symmetry in the crystal. The crystallographic refinement was facilitated in the early stages by using weak symmetry restraints and molecular dynamics. The R-factor including X-ray data to 1.83-A resolution was 21.1%. The final root mean square deviation from canonical values is 0.015 A for bond lengths and 3.2 degrees for bond angles. The resulting model of the tetramer includes independent coordinates for each of the four subunits allowing an internal check on the accuracy of the model. The crystalline mitochondrial malate dehydrogenase tetramer has been analyzed to determine the surface areas lost at different subunit-subunit interfaces. The results show that the interface with the largest surface area is the same one found in cytosolic malate dehydrogenase. Each of the subunits contains a bound citrate molecule in the active site permitting the elaboration of a model for substrate binding which agrees with that found for the crystalline enzyme from Escherichia coli. The environment of the N-terminal region of the crystallographic model has been studied because the functional protein is produced from a precursor. This precursor form has an additional 24 residues which are involved in mitochondrial targeting and, possibly, translocation. The crystallographic model of mitochondrial malate dehydrogenase has been compared with its cytosolic counterpart from porcine heart and two prokaryotic enzymes. Small but significant differences have been found in the polar versus nonpolar accessible surface areas between the mitochondrial and cytosolic enzymes. Using least squares methods, four different malate dehydrogenases have been superimposed and their consensus structure has been determined. An amino acid sequence alignment based on the crystallographic structures describes all the conserved positions. The consensus active site of these dicarboxylic acid dehydrogenases is derived from the least squares comparison.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17121853 J.B.Thoden, C.A.Sellick, R.J.Reece, and H.M.Holden (2007).
Understanding a transcriptional paradigm at the molecular level. The structure of yeast Gal80p.
  J Biol Chem, 282, 1534-1538.
PDB code: 2nvw
17499047 N.Elad, G.W.Farr, D.K.Clare, E.V.Orlova, A.L.Horwich, and H.R.Saibil (2007).
Topologies of a substrate protein bound to the chaperonin GroEL.
  Mol Cell, 26, 415-426.  
16541263 N.Zheng, B.Huang, J.Xu, S.Huang, J.Chen, X.Hu, K.Ying, and X.Yu (2006).
Enzymatic and physico-chemical characteristics of recombinant cMDH and mMDH of Clonorchis sinensis.
  Parasitol Res, 99, 174-180.  
16945919 S.Hara, K.Motohashi, F.Arisaka, P.G.Romano, N.Hosoya-Matsuda, N.Kikuchi, N.Fusada, and T.Hisabori (2006).
Thioredoxin-h1 reduces and reactivates the oxidized cytosolic malate dehydrogenase dimer in higher plants.
  J Biol Chem, 281, 32065-32071.  
15670147 B.Cox, M.M.Chit, T.Weaver, C.Gietl, J.Bailey, E.Bell, and L.Banaszak (2005).
Organelle and translocatable forms of glyoxysomal malate dehydrogenase. The effect of the N-terminal presequence.
  FEBS J, 272, 643-654.
PDB codes: 1sev 1smk
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.  
11964410 M.Knockaert, K.Wieking, S.Schmitt, M.Leost, K.M.Grant, J.C.Mottram, C.Kunick, and L.Meijer (2002).
Intracellular Targets of Paullones. Identification following affinity purification on immobilized inhibitor.
  J Biol Chem, 277, 25493-25501.  
11316888 J.Chen, and D.L.Smith (2001).
Amide hydrogen exchange shows that malate dehydrogenase is a folded monomer at pH 5.
  Protein Sci, 10, 1079-1083.  
10653644 D.Madern, C.Ebel, M.Mevarech, S.B.Richard, C.Pfister, and G.Zaccai (2000).
Insights into the molecular relationships between malate and lactate dehydrogenases: structural and biochemical properties of monomeric and dimeric intermediates of a mutant of tetrameric L-[LDH-like] malate dehydrogenase from the halophilic archaeon Haloarcula marismortui.
  Biochemistry, 39, 1001-1010.  
11054119 N.E.Labrou, D.J.Rigden, and Y.D.Clonis (2000).
Characterization of the NAD+ binding site of Candida boidinii formate dehydrogenase by affinity labelling and site-directed mutagenesis.
  Eur J Biochem, 267, 6657-6664.  
9893982 K.Shatalin, S.Lebreton, M.Rault-Leonardon, C.Vélot, and P.A.Srere (1999).
Electrostatic channeling of oxaloacetate in a fusion protein of porcine citrate synthase and porcine mitochondrial malate dehydrogenase.
  Biochemistry, 38, 881-889.  
10206992 S.Y.Kim, K.Y.Hwang, S.H.Kim, H.C.Sung, Y.S.Han, and Y.Cho (1999).
Structural basis for cold adaptation. Sequence, biochemical properties, and crystal structure of malate dehydrogenase from a psychrophile Aquaspirillium arcticum.
  J Biol Chem, 274, 11761-11767.
PDB codes: 1b8p 1b8u 1b8v
  9865953 J.E.Churchich (1998).
Recognition of partially-folded mitochondrial malate dehydrogenase by GroEL. Steady and time-dependent emission anisotropy measurements.
  Protein Sci, 7, 2587-2594.  
9692968 M.A.Jairajpuri, N.Azam, K.Baburaj, E.Bulliraju, and S.Durani (1998).
Charge and solvation effects in anion recognition centers: an inquiry exploiting reactive arginines.
  Biochemistry, 37, 10780-10791.  
9504803 N.Guex, and M.C.Peitsch (1997).
SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
  Electrophoresis, 18, 2714-2723.
PDB code: 2ak6
9210474 W.Li, and J.E.Churchich (1997).
Activation of partially folded mitochondrial malate dehydrogenase by thioredoxin.
  Eur J Biochem, 246, 127-132.  
8841108 A.H.Elcock, and J.A.McCammon (1996).
Evidence for electrostatic channeling in a fusion protein of malate dehydrogenase and citrate synthase.
  Biochemistry, 35, 12652-12658.  
8665917 M.Lemaire, M.Miginiac-Maslow, and P.Decottignies (1996).
The catalytic site of chloroplastic NADP-dependent malate dehydrogenase contains a His/Asp pair.
  Eur J Biochem, 236, 947-952.  
8998993 M.Ohkuma, K.Ohtoko, N.Takada, T.Hamamoto, R.Usami, T.Kudo, and K.Horikoshi (1996).
Characterization of malate dehydrogenase from deep-sea psychrophilic Vibrio sp. strain no. 5710 and cloning of its gene.
  FEMS Microbiol Lett, 137, 247-252.  
  7703849 D.R.Breiter, E.Resnik, and L.J.Banaszak (1994).
Engineering the quaternary structure of an enzyme: construction and analysis of a monomeric form of malate dehydrogenase from Escherichia coli.
  Protein Sci, 3, 2023-2032.  
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.