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PDBsum entry 9ldt

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protein ligands Protein-protein interface(s) links
Oxidoreductase(choh(d)-NAD+(a)) PDB id
9ldt
Jmol
Contents
Protein chains
332 a.a. *
Ligands
SO4 ×2
NAD ×2
OXM ×2
Waters ×153
* Residue conservation analysis
PDB id:
9ldt
Name: Oxidoreductase(choh(d)-NAD+(a))
Title: Design and synthesis of new enzymes based on the lactate deh framework
Structure: Lactate dehydrogenase. Chain: a, b. Engineered: yes
Source: Sus scrofa. Pig. Organism_taxid: 9823
Biol. unit: Tetramer (from PQS)
Resolution:
2.00Å     R-factor:   0.233    
Authors: C.R.Dunn,J.J.Holbrook,H.Muirhead
Key ref: C.R.Dunn et al. (1991). Design and synthesis of new enzymes based on the lactate dehydrogenase framework. Philos Trans R Soc Lond B Biol Sci, 332, 177-184. PubMed id: 1678537
Date:
26-Nov-91     Release date:   31-Oct-93    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00339  (LDHA_PIG) -  L-lactate dehydrogenase A chain
Seq:
Struc:
332 a.a.
331 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.1.1.1.27  - L-lactate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-lactate + NAD+ = pyruvate + NADH
(S)-lactate
Bound ligand (Het Group name = OXM)
matches with 71.43% 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     cilium   4 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
Philos Trans R Soc Lond B Biol Sci 332:177-184 (1991)
PubMed id: 1678537  
 
 
Design and synthesis of new enzymes based on the lactate dehydrogenase framework.
C.R.Dunn, H.M.Wilks, D.J.Halsall, T.Atkinson, A.R.Clarke, H.Muirhead, J.J.Holbrook.
 
  ABSTRACT  
 
Analysis of the mechanism and structure of lactate dehydrogenases is summarized in a map of the catalytic pathway. Chemical probes, single tryptophan residues inserted at specific sites and a crystal structure reveal slow movements of the protein framework that discriminate between closely related small substrates. Only small and correctly charged substrates allow the protein to engulf the substrate in an internal vacuole that is isolated from solvent protons, in which water is frozen and hydride transfer is rapid. The closed vacuole is very sensitive to the size and charge of the substrate and provides discrimination between small substrates that otherwise have too few functional groups to be distinguished at a solvated protein surface. This model was tested against its ability to successfully predict the design and synthesis of new enzymes such as L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase. Solvent friction limits the rate of forming the vacuole and thus the maximum rate of catalysis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18390601 H.Deng, S.Brewer, D.M.Vu, K.Clinch, R.Callender, and R.B.Dyer (2008).
On the pathway of forming enzymatically productive ligand-protein complexes in lactate dehydrogenase.
  Biophys J, 95, 804-813.  
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.  
17553776 H.O.Pörtner, L.Peck, and G.Somero (2007).
Thermal limits and adaptation in marine Antarctic ectotherms: an integrative view.
  Philos Trans R Soc Lond B Biol Sci, 362, 2233-2258.  
15879476 S.McClendon, D.M.Vu, K.Clinch, R.Callender, and R.B.Dyer (2005).
Structural transformations in the dynamics of Michaelis complex formation in lactate dehydrogenase.
  Biophys J, 89, L07-L09.  
11562945 F.Forcellino, and P.Derreumaux (2001).
Computer simulations aimed at structure prediction of supersecondary motifs in proteins.
  Proteins, 45, 159-166.  
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
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
  9568900 D.M.Lorber, and B.K.Shoichet (1998).
Flexible ligand docking using conformational ensembles.
  Protein Sci, 7, 938-950.  
9811833 G.O.Reznik, S.Vajda, T.Sano, and C.R.Cantor (1998).
A streptavidin mutant with altered ligand-binding specificity.
  Proc Natl Acad Sci U S A, 95, 13525-13530.  
9736762 P.A.Fields, and G.N.Somero (1998).
Hot spots in cold adaptation: localized increases in conformational flexibility in lactate dehydrogenase A4 orthologs of Antarctic notothenioid fishes.
  Proc Natl Acad Sci U S A, 95, 11476-11481.  
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.  
  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.  
  8528073 J.J.Onuffer, and J.F.Kirsch (1995).
Redesign of the substrate specificity of Escherichia coli aspartate aminotransferase to that of Escherichia coli tyrosine aminotransferase by homology modeling and site-directed mutagenesis.
  Protein Sci, 4, 1750-1757.  
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.  
  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.  
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.