spacer
spacer

PDBsum entry 5ldh

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
5ldh
Jmol
Contents
Protein chains
334 a.a. *
Ligands
LNC ×2
CIT ×2
* Residue conservation analysis
PDB id:
5ldh
Name: Oxidoreductase
Title: Structure of the active ternary complex of pig heart lactate dehydrogenase with s-lac-NAD at 2.7 angstroms resolution
Structure: Lactate dehydrogenase. Chain: a, b. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823
Biol. unit: Tetramer (from PQS)
Resolution:
2.70Å     R-factor:   0.196    
Authors: U.M.Grau,M.G.Rossmann
Key ref:
U.M.Grau et al. (1981). Structure of the active ternary complex of pig heart lactate dehydrogenase with S-lac-NAD at 2.7 A resolution. J Mol Biol, 151, 289-307. PubMed id: 7338899 DOI: 10.1016/0022-2836(81)90516-7
Date:
29-Oct-80     Release date:   04-Mar-81    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00336  (LDHB_PIG) -  L-lactate dehydrogenase B chain
Seq:
Struc:
334 a.a.
333 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 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 = CIT)
matches with 46.15% similarity
+ NAD(+)
= pyruvate
+
NADH
Bound ligand (Het Group name = LNC)
matches with 86.27% similarity
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     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/0022-2836(81)90516-7 J Mol Biol 151:289-307 (1981)
PubMed id: 7338899  
 
 
Structure of the active ternary complex of pig heart lactate dehydrogenase with S-lac-NAD at 2.7 A resolution.
U.M.Grau, W.E.Trommer, M.G.Rossmann.
 
  ABSTRACT  
 
No abstract given.

 
  Selected figure(s)  
 
Figure 8.
FIG:. 8. Superposition of'catalylically important residues the ni(wtinmide ring. and the substrate as bsrrved in pig , l,DHase/S-lac~~NAl)+ (double otline) and in the dogfish M LDHasr trmar? omplrs (open bonds).
 
  The above figure is reprinted by permission from Elsevier: J Mol Biol (1981, 151, 289-307) copyright 1981.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
17483170 J.R.Pineda, R.Callender, and S.D.Schwartz (2007).
Ligand binding and protein dynamics in lactate dehydrogenase.
  Biophys J, 93, 1474-1483.  
16444750 Z.M.Svedruzi─ç, and H.O.Spivey (2006).
Interaction between mammalian glyceraldehyde-3-phosphate dehydrogenase and L-lactate dehydrogenase from heart and muscle.
  Proteins, 63, 501-511.  
15634349 B.M.Martins, S.Macedo-Ribeiro, J.Bresser, W.Buckel, and A.Messerschmidt (2005).
Structural basis for stereo-specific catalysis in NAD(+)-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans.
  FEBS J, 272, 269-281.
PDB code: 1xdw
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.  
12419229 V.Kumar, J.E.Carlson, K.A.Ohgi, T.A.Edwards, D.W.Rose, C.R.Escalante, M.G.Rosenfeld, and A.K.Aggarwal (2002).
Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase.
  Mol Cell, 10, 857-869.
PDB code: 1mx3
11276087 J.A.Read, V.J.Winter, C.M.Eszes, R.B.Sessions, and R.L.Brady (2001).
Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase.
  Proteins, 43, 175-185.
PDB codes: 1i0z 1i10
11395412 J.J.Champoux (2001).
DNA topoisomerases: structure, function, and mechanism.
  Annu Rev Biochem, 70, 369-413.  
11451450 M.Graupner, and R.H.White (2001).
The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of the pro-4S hydrogen of NADH are found in the archaea.
  Biochim Biophys Acta, 1548, 169-173.  
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.  
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.  
10099612 N.E.Labrou, E.Eliopoulos, and Y.D.Clonis (1999).
Molecular modeling for the design of a biomimetic chimeric ligand. Application to the purification of bovine heart L-lactate dehydrogenase.
  Biotechnol Bioeng, 63, 322-332.  
10350459 T.Fujisawa, M.Kato, and Y.Inoko (1999).
Structural characterization of lactate dehydrogenase dissociation under high pressure studied by synchrotron high-pressure small-angle X-ray scattering.
  Biochemistry, 38, 6411-6418.  
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.  
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.  
9094207 R.L.Abu-Shumays, and J.W.Fristrom (1997).
IMP-L3, A 20-hydroxyecdysone-responsive gene encodes Drosophila lactate dehydrogenase: structural characterization and developmental studies.
  Dev Genet, 20, 11-22.  
8871566 S.Pietrokovski (1996).
Searching databases of conserved sequence regions by aligning protein multiple-alignments.
  Nucleic Acids Res, 24, 3836-3845.  
8626568 T.Bizouarn, C.Diggle, P.G.Quirk, R.L.Grimley, N.P.Cotton, C.M.Thomas, and J.B.Jackson (1996).
Interaction of nucleotides with the NAD(H)-binding domain of the proton-translocating transhydrogenase of Rhodospirillum rubrum.
  J Biol Chem, 271, 10103-10108.  
8591048 A.D.Cameron, I.Sinning, G.L'Hermite, B.Olin, P.G.Board, B.Mannervik, and T.A.Jones (1995).
Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate.
  Structure, 3, 717-727.
PDB codes: 1gsd 1gse 1gsf
7556167 C.Diggle, N.P.Cotton, R.L.Grimley, P.G.Quirk, C.M.Thomas, and J.B.Jackson (1995).
Conformational dynamics of a mobile loop in the NAD(H)-binding subunit of proton-translocating transhydrogenases from Rhodospirillum rubrum and Escherichia coli.
  Eur J Biochem, 232, 315-326.  
  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.  
8011065 D.J.Nicholls, M.Davey, S.E.Jones, J.Miller, J.J.Holbrook, A.R.Clarke, M.D.Scawen, T.Atkinson, and C.R.Goward (1994).
Substitution of the amino acid at position 102 with polar and aromatic residues influences substrate specificity of lactate dehydrogenase.
  J Protein Chem, 13, 129-133.  
8055963 I.K.Feil, H.P.Lerch, and D.Schomburg (1994).
Deletion variants of L-hydroxyisocaproate dehydrogenase. Probing substrate specificity.
  Eur J Biochem, 223, 857-863.  
  7849602 S.E.Brenner, and A.Berry (1994).
A quantitative methodology for the de novo design of proteins.
  Protein Sci, 3, 1871-1882.  
8436124 C.E.Voorter, L.T.Wintjes, P.W.Heinstra, H.Bloemendal, and W.W.De Jong (1993).
Comparison of stability properties of lactate dehydrogenase B4/epsilon-crystallin from different species.
  Eur J Biochem, 211, 643-648.  
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.  
8504833 J.Hendle, A.F.Bückmann, W.Aehle, D.Schomburg, and R.D.Schmid (1993).
Structure/activity relationship of adenine-modified NAD derivatives with respect to porcine heart lactate dehydrogenase isozyme H4 simulated with molecular mechanics.
  Eur J Biochem, 213, 947-956.  
8265562 M.Hilbert, G.Böhm, and R.Jaenicke (1993).
Structural relationships of homologous proteins as a fundamental principle in homology modeling.
  Proteins, 17, 138-151.  
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.  
1579570 A.J.Bauer, I.Rayment, P.A.Frey, and H.M.Holden (1992).
The molecular structure of UDP-galactose 4-epimerase from Escherichia coli determined at 2.5 A resolution.
  Proteins, 12, 372-381.
PDB code: 1udp
1572354 D.A.Fernández-Velasco, G.Garza-Ramos, L.Ramírez, L.Shoshani, A.Darszon, M.Tuena de Gómez-Puyou, and A.Gómez-Puyou (1992).
Activity of heart and muscle lactate dehydrogenases in all-aqueous systems and in organic solvents with low amounts of water. Effect of guanidine chloride.
  Eur J Biochem, 205, 501-508.  
1542673 D.W.Stock, and G.S.Whitt (1992).
Evolutionary implications of the cDNA sequence of the single lactate dehydrogenase of a lamprey.
  Proc Natl Acad Sci U S A, 89, 1799-1803.  
1620698 K.Huang, R.Kodandapani, H.Kallwass, J.K.Hogan, W.Parris, J.D.Friesen, M.Gold, J.B.Jones, and M.N.James (1992).
Crystallization and preliminary X-ray diffraction studies of two mutants of lactate dehydrogenase from Bacillus stearothermophilus.
  Proteins, 13, 158-161.  
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.  
1946424 D.Ghosh, C.M.Weeks, P.Grochulski, W.L.Duax, M.Erman, R.L.Rimsay, and J.C.Orr (1991).
Three-dimensional structure of holo 3 alpha,20 beta-hydroxysteroid dehydrogenase: a member of a short-chain dehydrogenase family.
  Proc Natl Acad Sci U S A, 88, 10064-10068.
PDB code: 1hsd
2044702 G.Pfleiderer, G.Nagel, and H.Bühler (1991).
Limited proteolysis of lactate dehydrogenase from porcine heart with trypsin: characterization and reactivation of the fragments.
  Experientia, 47, 470-475.  
2330370 K.Piontek, P.Chakrabarti, H.P.Schär, M.G.Rossmann, and H.Zuber (1990).
Structure determination and refinement of Bacillus stearothermophilus lactate dehydrogenase.
  Proteins, 7, 74-92.
PDB codes: 1ldb 2ldb
2658216 A.R.Clarke, T.Atkinson, and J.J.Holbrook (1989).
From analysis to synthesis: new ligand binding sites on the lactate dehydrogenase framework. Part I.
  Trends Biochem Sci, 14, 101-105.  
2543979 H.Deng, J.Zheng, J.Burgner, and R.Callender (1989).
Molecular properties of pyruvate bound to lactate dehydrogenase: a Raman spectroscopic study.
  Proc Natl Acad Sci U S A, 86, 4484-4488.  
3344288 B.Baumgarten, and J.Hönes (1988).
Spectroscopic investigation of dihydronicotinamides--II. Dihydronicotinamide adenine dinucleotide complexes with dehydrogenases.
  Photochem Photobiol, 47, 201-205.  
3061813 G.A.Reid, S.White, M.T.Black, F.Lederer, F.S.Mathews, and S.K.Chapman (1988).
Probing the active site of flavocytochrome b2 by site-directed mutagenesis.
  Eur J Biochem, 178, 329-333.  
3174623 W.Hendriks, J.W.Mulders, M.A.Bibby, C.Slingsby, H.Bloemendal, and W.W.de Jong (1988).
Duck lens epsilon-crystallin and lactate dehydrogenase B4 are identical: a single-copy gene product with two distinct functions.
  Proc Natl Acad Sci U S A, 85, 7114-7118.  
3796734 A.R.Clarke, D.B.Wigley, W.N.Chia, D.Barstow, T.Atkinson, and J.J.Holbrook (1986).
Site-directed mutagenesis reveals role of mobile arginine residue in lactate dehydrogenase catalysis.
  Nature, 324, 699-702.  
3856839 I.Fita, and M.G.Rossmann (1985).
The NADPH binding site on beef liver catalase.
  Proc Natl Acad Sci U S A, 82, 1604-1608.
PDB codes: 7cat 8cat
3971981 K.Okuda, I.Urabe, and H.Okada (1985).
Coenzymic activity of NADP derivatives alkylated at 2'-phosphate and 6-amino groups.
  Eur J Biochem, 147, 249-253.  
3996406 S.S.Li, H.F.Tiano, K.M.Fukasawa, K.Yagi, M.Shimizu, F.S.Sharief, Y.Nakashima, and Y.E.Pan (1985).
Protein structure and gene organization of mouse lactate dehydrogenase-A isozyme.
  Eur J Biochem, 149, 215-225.  
2411570 Z.A.Nagy, C.Servis, P.Walden, J.Klein, and E.Goldberg (1985).
Fine specificity analysis of lactate dehydrogenase B-specific proliferating T cell clones: implications for the mechanism of alloreactivity.
  Eur J Immunol, 15, 814-821.  
6411472 R.Hensel, U.Mayr, and C.Woenckhaus (1983).
Affinity labelling of the allosteric site of the L-lactate dehydrogenase of Lactobacillus casei.
  Eur J Biochem, 135, 359-365.  
6411465 R.Hensel, U.Mayr, and C.Y.Yang (1983).
The complete primary structure of the allosteric L-lactate dehydrogenase from Lactobacillus casei.
  Eur J Biochem, 134, 503-511.  
  6216447 C.M.Visser (1982).
Evolutionary roots of catalysis by nicotinamide and flavins in C-H oxidoreductases and in photosynthesis.
  Orig Life, 12, 165-179.  
6959107 J.J.Birktoft, R.T.Fernley, R.A.Bradshaw, and L.J.Banaszak (1982).
Amino acid sequence homology among the 2-hydroxy acid dehydrogenases: mitochondrial and cytoplasmic malate dehydrogenases form a homologous system with lactate dehydrogenase.
  Proc Natl Acad Sci U S A, 79, 6166-6170.  
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.