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PDBsum entry 2cmd

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Oxidoreductase(NAD(a)-choh(d)) PDB id
2cmd
Jmol
Contents
Protein chain
312 a.a. *
Ligands
CIT
Waters ×282
* Residue conservation analysis
PDB id:
2cmd
Name: Oxidoreductase(NAD(a)-choh(d))
Title: The crystal structure of e.Coli malate dehydrogenase: a complex of the apoenzyme and citrate at 1.87 angstroms resolution
Structure: Malate dehydrogenase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.87Å     R-factor:   0.188    
Authors: M.D.Hall,L.J.Banaszak
Key ref:
M.D.Hall et al. (1992). Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution. J Mol Biol, 226, 867-882. PubMed id: 1507230 DOI: 10.1016/0022-2836(92)90637-Y
Date:
23-Sep-92     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61889  (MDH_ECOLI) -  Malate dehydrogenase
Seq:
Struc:
312 a.a.
312 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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
Bound ligand (Het Group name = CIT)
matches with 69.00% similarity
+ NAD(+)
= oxaloacetate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     oxidation-reduction process   8 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/0022-2836(92)90637-Y J Mol Biol 226:867-882 (1992)
PubMed id: 1507230  
 
 
Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution.
M.D.Hall, D.G.Levitt, L.J.Banaszak.
 
  ABSTRACT  
 
The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.
 
  Selected figure(s)  
 
Figure 7.
Figure 7. Sp filfing model of' the NAI) vavit)~. (a) 7'hv tjop t~errodiagram represents n o~~arall \-iew of tlw KA41) (*:ivity with citrate in thi active site in a bac~kbone model of' the protein. All filled-in aeas belong to the (:a~i&y. (1)) The middle diagram represents a dose-up view of the X'AD binding wvity wit,h citrate in the active sit)e. All side-c:hnins ~II wntwt with the cavit,y are shown. (c) The bot,tom iagram represents the same feabres shown in (1)): ho\rrver. t'hr c*itrste has been c~hanged to rrpresent a malatr molrculc.
Figure 8.
Figure 8. Hypothetical model of P;AD in the active site of rMDHase. The stereodrawing shows the conformation of the XAD with malatr as found in the energy minimized structure of the eMDHase--NSD-malate complex. X&hods used to obtain this structure are described more fully in the text. Atoms involved in hydrogen bonding t,o the protein are labeled. Hydrogen bonds found between the malate and active site residues are shown by broken lines. 4 single heavy broken line drpic+s the trajectory of hydride ion transfer during catalysis.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 226, 867-882) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20419266 G.L.Martin, C.Lau, S.D.Minteer, and M.J.Cooney (2010).
Fluorescence analysis of chemical microenvironments and their impact upon performance of immobilized enzyme.
  Analyst, 135, 1131-1137.  
  19724119 J.Zaitseva, K.M.Meneely, and A.L.Lamb (2009).
Structure of Escherichia coli malate dehydrogenase at 1.45 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 866-869.
PDB code: 3hhp
17302428 M.Cha, E.J.Kim, H.Yun, B.K.Cho, and B.G.Kim (2007).
Synthesis of enantiopure (S)-2-hydroxyphenylbutanoic acid using novel hydroxy acid dehydrogenase from Enterobacter sp. BK2K.
  Biotechnol Prog, 23, 606-612.  
  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.  
17947381 Y.Yin, and J.F.Kirsch (2007).
Identification of functional paralog shift mutations: conversion of Escherichia coli malate dehydrogenase to a lactate dehydrogenase.
  Proc Natl Acad Sci U S A, 104, 17353-17357.  
16598154 R.Saito, C.Kato, and A.Nakayama (2006).
Amino acid substitutions in malate dehydrogenases of piezophilic bacteria isolated from intestinal contents of deep-sea fishes retrieved from the abyssal zone.
  J Gen Appl Microbiol, 52, 9.  
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.  
15043884 R.Saito, and A.Nakayama (2004).
Differences in malate dehydrogenases from the obligately piezophilic deep-sea bacterium Moritella sp. strain 2D2 and the psychrophilic bacterium Moritella sp. strain 5710.
  FEMS Microbiol Lett, 233, 165-172.  
12730240 N.Gibson, and L.McAlister-Henn (2003).
Physical and genetic interactions of cytosolic malate dehydrogenase with other gluconeogenic enzymes.
  J Biol Chem, 278, 25628-25636.  
  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.  
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.  
10194350 K.Johansson, S.Ramaswamy, M.Saarinen, M.Lemaire-Chamley, E.Issakidis-Bourguet, M.Miginiac-Maslow, and H.Eklund (1999).
Structural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form.
  Biochemistry, 38, 4319-4326.
PDB code: 7mdh
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
10076800 T.Neufeld, M.Eisenstein, K.A.Muszkat, and G.Fleminger (1998).
A citrate-binding site in calmodulin.
  J Mol Recognit, 11, 20-24.  
9843369 W.Wang, T.J.Kappock, J.Stubbe, and S.E.Ealick (1998).
X-ray crystal structure of glycinamide ribonucleotide synthetase from Escherichia coli.
  Biochemistry, 37, 15647-15662.
PDB code: 1gso
9188741 A.V.Efimov (1997).
Structural trees for protein superfamilies.
  Proteins, 28, 241-260.  
  8955383 K.Naterstad, V.Lauvrak, and R.Sirevåg (1996).
Malate dehydrogenase from the mesophile Chlorobium vibrioforme and from the mild thermophile Chlorobium tepidum: molecular cloning, construction of a hybrid, and expression in Escherichia coli.
  J Bacteriol, 178, 7047-7052.  
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.  
7647229 E.H.Muslin, D.Li, F.J.Stevens, M.Donnelly, M.Schiffer, and L.E.Anderson (1995).
Engineering a domain-locking disulfide into a bacterial malate dehydrogenase produces a redox-sensitive enzyme.
  Biophys J, 68, 2218-2223.  
  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.  
  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.  
8108402 E.F.Boyd, K.Nelson, F.S.Wang, T.S.Whittam, and R.K.Selander (1994).
Molecular genetic basis of allelic polymorphism in malate dehydrogenase (mdh) in natural populations of Escherichia coli and Salmonella enterica.
  Proc Natl Acad Sci U S A, 91, 1280-1284.  
8035212 S.D.Rufino, and T.L.Blundell (1994).
Structure-based identification and clustering of protein families and superfamilies.
  J Comput Aided Mol Des, 8, 5.  
8096339 D.J.Hartman, B.P.Surin, N.E.Dixon, N.J.Hoogenraad, and P.B.Høj (1993).
Substoichiometric amounts of the molecular chaperones GroEL and GroES prevent thermal denaturation and aggregation of mammalian mitochondrial malate dehydrogenase in vitro.
  Proc Natl Acad Sci U S A, 90, 2276-2280.  
  8331073 Y.Hashimoto, N.Li, H.Yokoyama, and T.Ezaki (1993).
Complete nucleotide sequence and molecular characterization of ViaB region encoding Vi antigen in Salmonella typhi.
  J Bacteriol, 175, 4456-4465.  
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.