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Oxidoreductase(choh(d)-NAD(a)) PDB id
1ldn
Jmol
Contents
Protein chains
(+ 2 more) 316 a.a. *
Ligands
FBP ×4
OXM ×8
NAD ×8
Waters ×572
* Residue conservation analysis
PDB id:
1ldn
Name: Oxidoreductase(choh(d)-NAD(a))
Title: Structure of a ternary complex of an allosteric lactate dehydrogenase from bacillus stearothermophilus at 2.5 angstroms resolution
Structure: L-lactate dehydrogenase. Chain: a, b, c, d, e, f, g, h. Engineered: yes
Source: Geobacillus stearothermophilus. Organism_taxid: 1422
Biol. unit: Tetramer (from PQS)
Resolution:
2.50Å     R-factor:   0.157    
Authors: D.B.Wigley,S.J.Gamblin,J.P.Turkenburg,E.J.Dodson,K.Piontek, H.Muirhead,J.J.Holbrook
Key ref: D.B.Wigley et al. (1992). Structure of a ternary complex of an allosteric lactate dehydrogenase from Bacillus stearothermophilus at 2.5 A resolution. J Mol Biol, 223, 317-335. PubMed id: 1731077 DOI: 10.1016/0022-2836(92)90733-Z
Date:
19-Nov-91     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00344  (LDH_GEOSE) -  L-lactate dehydrogenase
Seq:
Struc: 		317 a.a.
316 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.27  - L-lactate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-lactate + NAD+ = pyruvate + NADH
(S)-lactate
Bound ligand (Het Group name = OXM)
matches with 71.00% similarity 		+
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly 		= pyruvate
 + NADH
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   4 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/0022-2836(92)90733-Z J Mol Biol 223:317-335 (1992)
PubMed id: 1731077  
 
 
Structure of a ternary complex of an allosteric lactate dehydrogenase from Bacillus stearothermophilus at 2.5 A resolution.
D.B.Wigley, S.J.Gamblin, J.P.Turkenburg, E.J.Dodson, K.Piontek, H.Muirhead, J.J.Holbrook.
 
  ABSTRACT  
 
We report the refined structure of a ternary complex of an allosterically activated lactate dehydrogenase, including the important active site loop. Eightfold non-crystallographic symmetry averaging was utilized to improve the density maps. Interactions between the protein and bound coenzyme and oxamate are described in relation to other studies using site-specific mutagenesis. Fructose 1,6-bisphosphate (FruP2) is bound to the enzyme across one of the 2-fold axes of the tetramer, with the two phosphate moieties interacting with two anion binding sites, one on each of two subunits, across this interface. However, because FruP2 binds at this special site, yet does not possess an internal 2-fold symmetry axis, the ligand is statistically disordered and binds to each site in two different orientations. Binding of FruP2 to the tetramer is signalled to the active site principally through two interactions with His188 and Arg173. His188 is connected to His195 (which binds the carbonyl group of the substrate) and Arg173 is connected to Arg171 (the residue that binds the carboxylate group of the substrate).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18682365 S.Ferrer, I.Tuñón, V.Moliner, and I.H.Williams (2008).
Theoretical site-directed mutagenesis: Asp168Ala mutant of lactate dehydrogenase.
  J R Soc Interface, 5, S217-S224.  
17944947 P.Gaspar, A.R.Neves, C.A.Shearman, M.J.Gasson, A.M.Baptista, D.L.Turner, C.M.Soares, and H.Santos (2007).
The lactate dehydrogenases encoded by the ldh and ldhB genes in Lactococcus lactis exhibit distinct regulation and catalytic properties - comparative modeling to probe the molecular basis.
  FEBS J, 274, 5924-5936.  
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.  
15794574 F.Bernaudat, and L.Büllow (2005).
Rapid evaluation of nickel binding properties of His-tagged lactate dehydrogenases using surface plasmon resonance.
  J Chromatogr A, 1066, 219-224.  
16317459 S.Ferrer, E.Silla, I.Tuñón, M.Oliva, V.Moliner, and I.H.Williams (2005).
Dependence of enzyme reaction mechanism on protonation state of titratable residues and QM level description: lactate dehydrogenase.
  Chem Commun (Camb), 0, 5873-5875.  
  12392945 C.M.Halliwell, E.Simon, C.S.Toh, P.N.Bartlett, and A.E.Cass (2002).
A method for the determination of enzyme mass loading on an electrode surface through radioisotope labelling.
  Biosens Bioelectron, 17, 965-972.  
11807949 H.Uchikoba, S.Fushinobu, T.Wakagi, M.Konno, H.Taguchi, and H.Matsuzawa (2002).
Crystal structure of non-allosteric L-lactate dehydrogenase from Lactobacillus pentosus at 2.3 A resolution: specific interactions at subunit interfaces.
  Proteins, 46, 206-214.
PDB code: 1ez4
11876643 M.Gulotta, H.Deng, H.Deng, R.B.Dyer, and R.H.Callender (2002).
Toward an understanding of the role of dynamics on enzymatic catalysis in lactate dehydrogenase.
  Biochemistry, 41, 3353-3363.  
11114942 K.Arai, T.Kamata, H.Uchikoba, S.Fushinobu, H.Matsuzawa, and H.Taguchi (2001).
Some Lactobacillus L-lactate dehydrogenases exhibit comparable catalytic activities for pyruvate and oxaloacetate.
  J Bacteriol, 183, 397-400.  
10666635 B.I.Lee, C.Chang, S.J.Cho, G.W.Han, Y.G.Yu, S.H.Eom, and S.W.Suh (2000).
Lactate dehydrogenase from the hyperthermophilic archaeon Methanococcus jannaschii: overexpression, crystallization and preliminary X-ray analysis.
  Acta Crystallogr D Biol Crystallogr, 56, 81-83.  
10831409 C.D.Skory (2000).
Isolation and expression of lactate dehydrogenase genes from Rhizopus oryzae.
  Appl Environ Microbiol, 66, 2343-2348.  
10712593 S.Kochhar, V.S.Lamzin, A.Razeto, M.Delley, H.Hottinger, and J.E.Germond (2000).
Roles of his205, his296, his303 and Asp259 in catalysis by NAD+-specific D-lactate dehydrogenase.
  Eur J Biochem, 267, 1633-1639.  
9017191 J.van Beek, R.Callender, and M.R.Gunner (1997).
The contribution of electrostatic and van der Waals interactions to the stereospecificity of the reaction catalyzed by lactate dehydrogenase.
  Biophys J, 72, 619-626.  
  9212432 K.Savijoki, and A.Palva (1997).
Molecular genetic characterization of the L-lactate dehydrogenase gene (ldhL) of Lactobacillus helveticus and biochemical characterization of the enzyme.
  Appl Environ Microbiol, 63, 2850-2856.  
8901865 C.R.Dunn, M.J.Banfield, J.J.Barker, C.W.Higham, K.M.Moreton, D.Turgut-Balik, R.L.Brady, and J.J.Holbrook (1996).
The structure of lactate dehydrogenase from Plasmodium falciparum reveals a new target for anti-malarial design.
  Nat Struct Biol, 3, 912-915.
PDB code: 1ldg
  8732758 R.Ostendorp, G.Auerbach, and R.Jaenicke (1996).
Extremely thermostable L(+)-lactate dehydrogenase from Thermotoga maritima: cloning, characterization, and crystallization of the recombinant enzyme in its tetrameric and octameric state.
  Protein Sci, 5, 862-873.  
  8925837 T.Dams, R.Ostendorp, M.Ott, K.Rutkat, and R.Jaenicke (1996).
Tetrameric and octameric lactate dehydrogenase from the hyperthermophilic bacterium Thermotoga maritima. Structure and stability of the two active forms.
  Eur J Biochem, 240, 274-279.  
  7539419 D.Garmyn, T.Ferain, N.Bernard, P.Hols, B.Delplace, and J.Delcour (1995).
Pediococcus acidilactici ldhD gene: cloning, nucleotide sequence, and transcriptional analysis.
  J Bacteriol, 177, 3427-3437.  
  7887607 D.Garmyn, T.Ferain, N.Bernard, P.Hols, and J.Delcour (1995).
Cloning, nucleotide sequence, and transcriptional analysis of the Pediococcus acidilactici L-(+)-lactate dehydrogenase gene.
  Appl Environ Microbiol, 61, 266-272.  
  7764905 A.S.el Hawrani, K.M.Moreton, R.B.Sessions, A.R.Clarke, and J.J.Holbrook (1994).
Engineering surface loops of proteins--a preferred strategy for obtaining new enzyme function.
  Trends Biotechnol, 12, 207-211.  
  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.  
7858977 M.Xie, J.Seravalli, W.P.Huskey, K.B.Schowen, and R.L.Schowen (1994).
Solvent isotope effects and the nature of electrophilic catalysis in the action of the lactate dehydrogenase of Bacillus stearothermophilus.
  Bioorg Med Chem, 2, 691-695.  
8444183 D.J.Nicholls, I.S.Wood, T.J.Nobbs, A.R.Clarke, J.J.Holbrook, T.Atkinson, and M.D.Scawen (1993).
Dissecting the contributions of a specific side-chain interaction to folding and catalysis of Bacillus stearothermophilus lactate dehydrogenase.
  Eur J Biochem, 212, 447-455.  
  1304374 A.Cortes, D.C.Emery, D.J.Halsall, R.M.Jackson, A.R.Clarke, and J.J.Holbrook (1992).
Charge balance in the alpha-hydroxyacid dehydrogenase vacuole: an acid test.
  Protein Sci, 1, 892-901.  
1476393 H.M.Wilks, A.Cortes, D.C.Emery, D.J.Halsall, A.R.Clarke, and J.J.Holbrook (1992).
Opportunities and limits in creating new enzymes. Experiences with the NAD-dependent lactate dehydrogenase frameworks of humans and bacteria.
  Ann N Y Acad Sci, 672, 80-93.  
1425707 H.Taguchi, and T.Ohta (1992).
Unusual amino acid substitution in the anion-binding site of Lactobacillus plantarum non-allosteric L-lactate dehydrogenase.
  Eur J Biochem, 209, 993-998.  
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.  
1396685 S.Kochhar, H.Hottinger, N.Chuard, P.G.Taylor, T.Atkinson, M.D.Scawen, and D.J.Nicholls (1992).
Cloning and overexpression of Lactobacillus helveticus D-lactate dehydrogenase gene in Escherichia coli.
  Eur J Biochem, 208, 799-805.  
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.