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PDBsum entry 1bdm

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Oxidoreductase(NAD(a)-choh(d)) PDB id
1bdm
Jmol
Contents
Protein chains
318 a.a. *
Ligands
NAX ×2
Waters ×202
* Residue conservation analysis
PDB id:
1bdm
Name: Oxidoreductase(NAD(a)-choh(d))
Title: The structure at 1.8 angstroms resolution of a single site mutant (t189i) of malate dehydrogenase from thermus flavus with increased enzymatic activity
Structure: Malate dehydrogenase. Chain: a, b. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 274.
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.169    
Authors: C.A.Kelly,J.J.Birktoft
Key ref:
C.A.Kelly et al. (1993). Determinants of protein thermostability observed in the 1.9-A crystal structure of malate dehydrogenase from the thermophilic bacterium Thermus flavus. Biochemistry, 32, 3913-3922. PubMed id: 8471603 DOI: 10.1021/bi00066a010
Date:
16-Feb-93     Release date:   20-Dec-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P10584  (MDH_THETH) -  Malate dehydrogenase
Seq:
Struc:
327 a.a.
318 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
+
NAD(+)
Bound ligand (Het Group name = NAX)
matches with 97.00% similarity
= oxaloacetate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi00066a010 Biochemistry 32:3913-3922 (1993)
PubMed id: 8471603  
 
 
Determinants of protein thermostability observed in the 1.9-A crystal structure of malate dehydrogenase from the thermophilic bacterium Thermus flavus.
C.A.Kelly, M.Nishiyama, Y.Ohnishi, T.Beppu, J.J.Birktoft.
 
  ABSTRACT  
 
A binary complex of malate dehydrogenase from the thermophilic bacterium Thermus flavus (tMDH) with NADH has been crystallized from poly(ethylene glycol) 3500, pH 8.5, yielding diffraction-quality crystals in space group P2(1)2(1)2(1). The structure was solved at 1.9-A resolution using molecular replacement and refined to an R factor of 15.8% with good geometry. The primary sequence of tMDH is 55% identical to that of cytoplasmic malate dehydrogenase (cMDH) [Birktoft, J. J., Rhodes, G., & Banaszak, L. J. (1989) Biochemistry 28, 6065-6081], and overall their three-dimensional structures are very similar. Like cMDH, tMDH crystallized as a dimer with one coenzyme bound per subunit. The coenzyme binds in the extended conformation, and most of the interactions with enzyme are similar to those in cMDH. In tMDH, small local conformational changes are caused by the replacement of a glutamic acid for the aspartic acid involved in hydrogen bonding to the adenine ribose of NADH. Comparison of tMDH with cMDH reveals that both tMDH subunits more closely resemble the B subunit of cMDH which therefore is the more likely representative of the solution conformation. While cMDH is inactivated at temperatures above about 50 degrees C, tMDH is fully active at 90 degrees C. On the basis of the X-ray crystal structure, a number of factors have been identified which are likely to contribute to the relative thermostability of tMDH compared to cMDH. The most striking of the differences involves the introduction of four ion pairs per monomer. All of these ion pairs are solvent-accessible. Three of these ion pairs are located in the dimer interface, Glu27-Lys31, Glu57-Lys168, and Glu57-Arg229, and one ion pair, Glu275-Arg149, is at the domain interface within each subunit. Additionally, we observe incorporation of additional alanines into alpha-helices of tMDH and, in one instance, incorporation of an aspartate that functions as a counterchange to an alpha-helix dipole. The possible contributions of these and other factors to protein thermostability in tMDH are discussed.
 

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.  
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.  
17625021 J.S.Byun, J.K.Rhee, N.D.Kim, J.Yoon, D.U.Kim, E.Koh, J.W.Oh, and H.S.Cho (2007).
Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties.
  BMC Struct Biol, 7, 47.
PDB code: 2c7b
  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.  
17089214 E.Issakidis-Bourguet, D.Lavergne, X.Trivelli, P.Decottignies, and M.Miginiac-Maslow (2006).
Transferring redox regulation properties from sorghum NADP-malate dehydrogenase to Thermus NAD-malate dehydrogenase.
  Photosynth Res, 89, 213-223.  
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.  
16960374 T.Tomita, T.Kuzuyama, and M.Nishiyama (2006).
Alteration of coenzyme specificity of lactate dehydrogenase from Thermus thermophilus by introducing the loop region of NADP(H)-dependent malate dehydrogenase.
  Biosci Biotechnol Biochem, 70, 2230-2235.  
15856483 F.Rodier, R.P.Bahadur, P.Chakrabarti, and J.Janin (2005).
Hydration of protein-protein interfaces.
  Proteins, 60, 36-45.  
15265031 A.P.Maloney, S.M.Callan, P.G.Murray, and M.G.Tuohy (2004).
Mitochondrial malate dehydrogenase from the thermophilic, filamentous fungus Talaromyces emersonii.
  Eur J Biochem, 271, 3115-3126.  
14695284 B.Liu, M.Bartlam, R.Gao, W.Zhou, H.Pang, Y.Liu, Y.Feng, and Z.Rao (2004).
Crystal structure of the hyperthermophilic inorganic pyrophosphatase from the archaeon Pyrococcus horikoshii.
  Biophys J, 86, 420-427.
PDB code: 1ude
14660666 F.Febbraio, A.Andolfo, F.Tanfani, R.Briante, F.Gentile, S.Formisano, C.Vaccaro, A.Scirè, E.Bertoli, P.Pucci, and R.Nucci (2004).
Thermal stability and aggregation of sulfolobus solfataricus beta-glycosidase are dependent upon the N-epsilon-methylation of specific lysyl residues: critical role of in vivo post-translational modifications.
  J Biol Chem, 279, 10185-10194.  
15494440 R.I.Dima, and D.Thirumalai (2004).
Probing the instabilities in the dynamics of helical fragments from mouse PrPC.
  Proc Natl Acad Sci U S A, 101, 15335-15340.  
12382287 C.Charron, B.Vitoux, and A.Aubry (2002).
Comparative analysis of thermoadaptation within the archaeal glyceraldehyde-3-phosphate dehydrogenases from mesophilic Methanobacterium bryantii and thermophilic Methanothermus fervidus.
  Biopolymers, 65, 263-273.  
  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.  
12213823 F.Gentile, P.Amodeo, F.Febbraio, F.Picaro, A.Motta, S.Formisano, and R.Nucci (2002).
SDS-resistant active and thermostable dimers are obtained from the dissociation of homotetrameric beta-glycosidase from hyperthermophilic Sulfolobus solfataricus in SDS. Stabilizing role of the A-C intermonomeric interface.
  J Biol Chem, 277, 44050-44060.  
11551792 A.Karshikoff, and R.Ladenstein (2001).
Ion pairs and the thermotolerance of proteins from hyperthermophiles: a "traffic rule" for hot roads.
  Trends Biochem Sci, 26, 550-556.  
11391775 C.A.Olson, E.J.Spek, Z.Shi, A.Vologodskii, and N.R.Kallenbach (2001).
Cooperative helix stabilization by complex Arg-Glu salt bridges.
  Proteins, 44, 123-132.  
11488906 K.Shiraki, S.Nishikori, S.Fujiwara, H.Hashimoto, Y.Kai, M.Takagi, and T.Imanaka (2001).
Comparative analyses of the conformational stability of a hyperthermophilic protein and its mesophilic counterpart.
  Eur J Biochem, 268, 4144-4150.  
10801491 A.Szilágyi, and P.Závodszky (2000).
Structural differences between mesophilic, moderately thermophilic and extremely thermophilic protein subunits: results of a comprehensive survey.
  Structure, 8, 493-504.  
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.  
10679894 P.E.Smith, and J.J.Tanner (2000).
Conformations of nicotinamide adenine dinucleotide (NAD(+)) in various environments.
  J Mol Recognit, 13, 27-34.  
10651277 C.Li, J.Heatwole, S.Soelaiman, and M.Shoham (1999).
Crystal structure of a thermophilic alcohol dehydrogenase substrate complex suggests determinants of substrate specificity and thermostability.
  Proteins, 37, 619-627.
PDB code: 1bxz
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
10497207 P.J.Haney, M.Stees, and J.Konisky (1999).
Analysis of thermal stabilizing interactions in mesophilic and thermophilic adenylate kinases from the genus Methanococcus.
  J Biol Chem, 274, 28453-28458.  
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
10029535 T.Nakai, K.Okada, S.Akutsu, I.Miyahara, S.Kawaguchi, R.Kato, S.Kuramitsu, and K.Hirotsu (1999).
Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate.
  Biochemistry, 38, 2413-2424.
PDB codes: 1bjw 1bkg
  10417229 Y.Korkhin, A.J.Kalb (Gilboa), M.Peretz, O.Bogin, Y.Burstein, and F.Frolow (1999).
Oligomeric integrity--the structural key to thermal stability in bacterial alcohol dehydrogenases.
  Protein Sci, 8, 1241-1249.  
9837927 E.Ruelland, K.Johansson, P.Decottignies, N.Djukic, and M.Miginiac-Maslow (1998).
The autoinhibition of sorghum NADP malate dehydrogenase is mediated by a C-terminal negative charge.
  J Biol Chem, 273, 33482-33488.  
9849940 J.Sanz-Aparicio, J.A.Hermoso, M.Martínez-Ripoll, B.González, C.López-Camacho, and J.Polaina (1998).
Structural basis of increased resistance to thermal denaturation induced by single amino acid substitution in the sequence of beta-glucosidase A from Bacillus polymyxa.
  Proteins, 33, 567-576.
PDB code: 1e4i
9893953 R.Scandurra, V.Consalvi, R.Chiaraluce, L.Politi, and P.C.Engel (1998).
Protein thermostability in extremophiles.
  Biochimie, 80, 933-941.  
9657695 S.Aono, D.Bentrop, I.Bertini, A.Donaire, C.Luchinat, Y.Niikura, and A.Rosato (1998).
Solution structure of the oxidized Fe7S8 ferredoxin from the thermophilic bacterium Bacillus schlegelii by 1H NMR spectroscopy.
  Biochemistry, 37, 9812-9826.
PDB codes: 1bc6 1bd6
9501170 V.Villeret, B.Clantin, C.Tricot, C.Legrain, M.Roovers, V.Stalon, N.Glansdorff, and J.Van Beeumen (1998).
The crystal structure of Pyrococcus furiosus ornithine carbamoyltransferase reveals a key role for oligomerization in enzyme stability at extremely high temperatures.
  Proc Natl Acad Sci U S A, 95, 2801-2806.
PDB code: 1a1s
9672043 X.Barril, C.Alemán, M.Orozco, and F.J.Luque (1998).
Salt bridge interactions: stability of the ionic and neutral complexes in the gas phase, in solution, and in proteins.
  Proteins, 32, 67-79.  
9371755 B.J.Bahnson, T.D.Colby, J.K.Chin, B.M.Goldstein, and J.P.Klinman (1997).
A link between protein structure and enzyme catalyzed hydrogen tunneling.
  Proc Natl Acad Sci U S A, 94, 12797-12802.
PDB codes: 1axe 1axg
  9336832 C.E.Bell, T.O.Yeates, and D.Eisenberg (1997).
Unusual conformation of nicotinamide adenine dinucleotide (NAD) bound to diphtheria toxin: a comparison with NAD bound to the oxidoreductase enzymes.
  Protein Sci, 6, 2084-2096.  
  9165087 L.Prade, P.Hof, and B.Bieseler (1997).
Dimer interface of glutathione S-transferase from Arabidopsis thaliana: influence of the G-site architecture on the dimer interface and implications for classification.
  Biol Chem, 378, 317-320.  
9166771 M.Hennig, R.Sterner, K.Kirschner, and J.N.Jansonius (1997).
Crystal structure at 2.0 A resolution of phosphoribosyl anthranilate isomerase from the hyperthermophile Thermotoga maritima: possible determinants of protein stability.
  Biochemistry, 36, 6009-6016.
PDB code: 1nsj
  9171389 M.Van de Casteele, P.Chen, M.Roovers, C.Legrain, and N.Glansdorff (1997).
Structure and expression of a pyrimidine gene cluster from the extreme thermophile Thermus strain ZO5.
  J Bacteriol, 179, 3470-3481.  
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
9144797 P.Haney, J.Konisky, K.K.Koretke, Z.Luthey-Schulten, and P.G.Wolynes (1997).
Structural basis for thermostability and identification of potential active site residues for adenylate kinases from the archaeal genus Methanococcus.
  Proteins, 28, 117-130.  
9195883 U.Ermler, M.Merckel, R.Thauer, and S.Shima (1997).
Formylmethanofuran: tetrahydromethanopterin formyltransferase from Methanopyrus kandleri - new insights into salt-dependence and thermostability.
  Structure, 5, 635-646.
PDB code: 1ftr
8639325 D.W.Rice, K.S.Yip, T.J.Stillman, K.L.Britton, A.Fuentes, I.Connerton, A.Pasquo, R.Scandura, and P.C.Engel (1996).
Insights into the molecular basis of thermal stability from the structure determination of Pyrococcus furiosus glutamate dehydrogenase.
  FEMS Microbiol Rev, 18, 105-117.  
8647119 H.Sticht, G.Wildegger, D.Bentrop, B.Darimont, R.Sterner, and P.Rösch (1996).
An NMR-derived model for the solution structure of oxidized Thermotoga maritima 1[Fe4-S4] ferredoxin.
  Eur J Biochem, 237, 726-735.
PDB code: 1rof
8611563 J.J.Tanner, R.M.Hecht, and K.L.Krause (1996).
Determinants of enzyme thermostability observed in the molecular structure of Thermus aquaticus D-glyceraldehyde-3-phosphate dehydrogenase at 25 Angstroms Resolution.
  Biochemistry, 35, 2597-2609.
PDB code: 1cer
  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.  
8939753 S.Macedo-Ribeiro, B.Darimont, R.Sterner, and R.Huber (1996).
Small structural changes account for the high thermostability of 1[4Fe-4S] ferredoxin from the hyperthermophilic bacterium Thermotoga maritima.
  Structure, 4, 1291-1301.
PDB code: 1vjw
8591026 K.S.Yip, T.J.Stillman, K.L.Britton, P.J.Artymiuk, P.J.Baker, S.E.Sedelnikova, P.C.Engel, A.Pasquo, R.Chiaraluce, and V.Consalvi (1995).
The structure of Pyrococcus furiosus glutamate dehydrogenase reveals a key role for ion-pair networks in maintaining enzyme stability at extreme temperatures.
  Structure, 3, 1147-1158.
PDB codes: 1gtm 1hrd
  8580851 L.F.Delboni, S.C.Mande, F.Rentier-Delrue, V.Mainfroid, S.Turley, F.M.Vellieux, J.A.Martial, and W.G.Hol (1995).
Crystal structure of recombinant triosephosphate isomerase from Bacillus stearothermophilus. An analysis of potential thermostability factors in six isomerases with known three-dimensional structures points to the importance of hydrophobic interactions.
  Protein Sci, 4, 2594-2604.
PDB code: 1btm
8747456 M.Hennig, B.Darimont, R.Sterner, K.Kirschner, and J.N.Jansonius (1995).
2.0 A structure of indole-3-glycerol phosphate synthase from the hyperthermophile Sulfolobus solfataricus: possible determinants of protein stability.
  Structure, 3, 1295-1306.
PDB code: 1igs
  8535242 P.Shih, and J.F.Kirsch (1995).
Design and structural analysis of an engineered thermostable chicken lysozyme.
  Protein Sci, 4, 2063-2072.  
7579645 R.J.Russell, and G.L.Taylor (1995).
Engineering thermostability: lessons from thermophilic proteins.
  Curr Opin Biotechnol, 6, 370-374.  
  7556082 R.Sterner, A.Dahm, B.Darimont, A.Ivens, W.Liebl, and K.Kirschner (1995).
(Beta alpha)8-barrel proteins of tryptophan biosynthesis in the hyperthermophile Thermotoga maritima.
  EMBO J, 14, 4395-4402.  
  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.  
  8251931 S.F.Betz (1993).
Disulfide bonds and the stability of globular proteins.
  Protein Sci, 2, 1551-1558.  
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.