spacer
spacer

PDBsum entry 4mdh

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase(NAD(a)-choh(d)) PDB id
4mdh
Jmol
Contents
Protein chains
334 a.a. *
Ligands
SO4 ×2
NAD ×2
Waters ×471
* Residue conservation analysis
PDB id:
4mdh
Name: Oxidoreductase(NAD(a)-choh(d))
Title: Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-angstroms resolution
Structure: Cytoplasmic malate dehydrogenase. Chain: a, b. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.167    
Authors: J.J.Birktoft,L.J.Banaszak
Key ref:
J.J.Birktoft et al. (1989). Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A resolution. Biochemistry, 28, 6065-6081. PubMed id: 2775751 DOI: 10.1021/bi00440a051
Date:
12-Apr-89     Release date:   19-Apr-89    
Supersedes: 2mdh
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11708  (MDHC_PIG) -  Malate dehydrogenase, cytoplasmic
Seq:
Struc:
334 a.a.
333 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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 = NAD)
corresponds exactly
= oxaloacetate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi00440a051 Biochemistry 28:6065-6081 (1989)
PubMed id: 2775751  
 
 
Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A resolution.
J.J.Birktoft, G.Rhodes, L.J.Banaszak.
 
  ABSTRACT  
 
The molecular structure of cytoplasmic malate dehydrogenase from pig heart has been refined by alternating rounds of restrained least-squares methods and model readjustment on an interactive graphics system. The resulting structure contains 333 amino acids in each of the two subunits, 2 NAD molecules, 471 solvent molecules, and 2 large noncovalently bound molecules that are assumed to be sulfate ions. The crystallographic study was done on one entire dimer without symmetry restraints. Analysis of the relative position of the two subunits shows that the dimer does not obey exact 2-fold rotational symmetry; instead, the subunits are related by a 173 degrees rotation. The structure results in a R factor of 16.7% for diffraction data between 6.0 and 2.5 A, and the rms deviations from ideal bond lengths and angles are 0.017 A and 2.57 degrees, respectively. The bound coenzyme in addition to hydrophobic interactions makes numerous hydrogen bonds that either are directly between NAD and the enzyme or are with solvent molecules, some of which in turn are hydrogen bonded to the enzyme. The carboxamide group of NAD is hydrogen bonded to the side chain of Asn-130 and via a water molecule to the backbone nitrogens of Leu-157 and Asp-158 and to the carbonyl oxygen of Leu-154. Asn-130 is one of the corner residues in a beta-turn that contains the lone cis peptide bond in cytoplasmic malate dehydrogenase, situated between Asn-130 and Pro-131. The active site histidine, His-186, is hydrogen bonded from nitrogen ND1 to the carboxylate of Asp-158 and from its nitrogen NE2 to the sulfate ion bound in the putative substrate binding site. In addition to interacting with the active site histidine, this sulfate ion is also hydrogen bonded to the guanidinium group of Arg-161, to the carboxamide group of Asn-140, and to the hydroxyl group of Ser-241. It is speculated that the substrate, malate or oxaloacetate, is bound in the sulfate binding site with the substrate 1-carboxyl hydrogen bonded to the guanidinium group of Arg-161.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20122196 P.Sundaramurthy, K.Shameer, R.Sreenivasan, S.Gakkhar, and R.Sowdhamini (2010).
HORI: a web server to compute Higher Order Residue Interactions in protein structures.
  BMC Bioinformatics, 11, S24.  
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.  
19551876 R.Nian, D.S.Kim, L.Tan, C.W.Kim, and W.S.Choe (2009).
Synergistic coordination of polyethylene glycol with ClpB/DnaKJE bichaperone for refolding of heat-denatured malate dehydrogenase.
  Biotechnol Prog, 25, 1078-1085.  
18006497 X.Ma, N.Sayed, P.Baskaran, A.Beuve, and F.van den Akker (2008).
PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure.
  J Biol Chem, 283, 1167-1178.
PDB codes: 2p04 2p08
17419765 M.S.Jang, N.Y.Kang, K.S.Kim, C.H.Kim, J.H.Lee, and Y.C.Lee (2007).
Mutational analysis of NADH-binding residues in triphenylmethane reductase from Citrobacter sp. strain KCTC 18061P.
  FEMS Microbiol Lett, 271, 78-82.  
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.  
16332773 M.S.Jang, Y.M.Lee, C.H.Kim, J.H.Lee, D.W.Kang, S.J.Kim, and Y.C.Lee (2005).
Triphenylmethane reductase from Citrobacter sp. strain KCTC 18061P: purification, characterization, gene cloning, and overexpression of a functional protein in Escherichia coli.
  Appl Environ Microbiol, 71, 7955-7960.  
15331786 J.Luo, and T.C.Bruice (2004).
Anticorrelated motions as a driving force in enzyme catalysis: the dehydrogenase reaction.
  Proc Natl Acad Sci U S A, 101, 13152-13156.  
12037302 A.C.Hausrath, and B.W.Matthews (2002).
Thermolysin in the absence of substrate has an open conformation.
  Acta Crystallogr D Biol Crystallogr, 58, 1002-1007.
PDB code: 1l3f
  12113928 C.O.Brämer, and A.Steinbüchel (2002).
The malate dehydrogenase of Ralstonia eutropha and functionality of the C(3)/C(4) metabolism in a Tn5-induced mdh mutant.
  FEMS Microbiol Lett, 212, 159-164.  
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.  
12153583 S.C.Sanyal, D.Bhattacharyya, and C.Das Gupta (2002).
The folding of dimeric cytoplasmic malate dehydrogenase. Equilibrium and kinetic studies.
  Eur J Biochem, 269, 3856-3866.  
12034826 S.C.Sanyal, S.Pal, S.Chowdhury, C.DasGupta, and S.Chaudhuri (2002).
23S rRNA assisted folding of cytoplasmic malate dehydrogenase is distinctly different from its self-folding.
  Nucleic Acids Res, 30, 2390-2397.  
  10933503 A.F.Monzingo, A.Breksa, S.Ernst, D.R.Appling, and J.D.Robertus (2000).
The X-ray structure of the NAD-dependent 5,10-methylenetetrahydrofolate dehydrogenase from Saccharomyces cerevisiae.
  Protein Sci, 9, 1374-1381.
PDB codes: 1edz 1ee9
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.  
10339579 G.Wu, A.Fiser, B.ter Kuile, A.Sali, and M.Müller (1999).
Convergent evolution of Trichomonas vaginalis lactate dehydrogenase from malate dehydrogenase.
  Proc Natl Acad Sci U S A, 96, 6285-6290.  
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
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.  
9519408 M.Allaire, Y.Li, R.E.MacKenzie, and M.Cygler (1998).
The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional enzyme at 1.5 A resolution.
  Structure, 6, 173-182.
PDB code: 1a4i
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
  8901548 D.Płochocka, M.Wełnicki, P.Zielenkiewicz, and W.Ostoja-Zagórski (1996).
Three-dimensional model of the potyviral genome-linked protein.
  Proc Natl Acad Sci U S A, 93, 12150-12154.  
8724970 J.L.Weller, H.Jaffe, P.H.Roseboom, M.J.Zylka, and D.C.Klein (1996).
2D-PAGE analysis: adrenergically regulated pineal protein AIP 37/6 is a phosphorylated isoform of cytosolic malate dehydrogenase.
  Brain Res, 713, 8.  
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.  
8611656 M.M.Heath, K.C.Rixon, and J.J.Harding (1996).
Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, alpha-crystallin.
  Biochim Biophys Acta, 1315, 176-184.  
8672472 N.Tanaka, T.Nonaka, T.Tanabe, T.Yoshimoto, D.Tsuru, and Y.Mitsui (1996).
Crystal structures of the binary and ternary complexes of 7 alpha-hydroxysteroid dehydrogenase from Escherichia coli.
  Biochemistry, 35, 7715-7730.
PDB codes: 1ahh 1ahi 1fmc
  8563637 R.M.Stroud, and E.B.Fauman (1995).
Significance of structural changes in proteins: expected errors in refined protein structures.
  Protein Sci, 4, 2392-2404.  
  7849603 C.R.Goward, and D.J.Nicholls (1994).
Malate dehydrogenase: a model for structure, evolution, and catalysis.
  Protein Sci, 3, 1883-1888.  
8076646 C.R.Goward, J.Miller, D.J.Nicholls, L.I.Irons, M.D.Scawen, R.O'Brien, and B.Z.Chowdhry (1994).
A single amino acid mutation enhances the thermal stability of Escherichia coli malate dehydrogenase.
  Eur J Biochem, 224, 249-255.  
7918997 D.Li, F.J.Stevens, M.Schiffer, and L.E.Anderson (1994).
Mechanism of light modulation: identification of potential redox-sensitive cysteines distal to catalytic site in light-activated chloroplast enzymes.
  Biophys J, 67, 29-35.  
  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.  
7937764 K.S.Quandt, and D.E.Hultquist (1994).
Flavin reductase: sequence of cDNA from bovine liver and tissue distribution.
  Proc Natl Acad Sci U S A, 91, 9322-9326.  
7881907 P.Rowland, A.K.Basak, S.Gover, H.R.Levy, and M.J.Adams (1994).
The three-dimensional structure of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides refined at 2.0 A resolution.
  Structure, 2, 1073-1087.
PDB code: 1dpg
7664032 V.S.Lamzin, Z.Dauter, and K.S.Wilson (1994).
Dehydrogenation through the looking-glass.
  Nat Struct Biol, 1, 281-282.  
  8298462 M.B.Swindells (1993).
Classification of doubly wound nucleotide binding topologies using automated loop searches.
  Protein Sci, 2, 2146-2153.  
8464727 S.L.Moodie, and J.M.Thornton (1993).
A study into the effects of protein binding on nucleotide conformation.
  Nucleic Acids Res, 21, 1369-1380.  
  1735722 C.Charnock, U.H.Refseth, and R.Sirevåg (1992).
Malate dehydrogenase from Chlorobium vibrioforme, Chlorobium tepidum, and Heliobacterium gestii: purification, characterization, and investigation of dinucleotide binding by dehydrogenases by use of empirical methods of protein sequence analysis.
  J Bacteriol, 174, 1307-1313.  
1358610 K.L.Britton, P.J.Baker, D.W.Rice, and T.J.Stillman (1992).
Structural relationship between the hexameric and tetrameric family of glutamate dehydrogenases.
  Eur J Biochem, 209, 851-859.  
1409577 R.B.Russell, and G.J.Barton (1992).
Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels.
  Proteins, 14, 309-323.  
1583536 R.M.Jackson, R.B.Sessions, and J.J.Holbrook (1992).
A prediction of the three-dimensional structure of maize NADP(+)-dependent malate dehydrogenase which explains aspects of light-dependent regulation unique to plant enzymes.
  J Comput Aided Mol Des, 6, 1.  
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.