PDBsum entry 1lth

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Oxidoreductase PDB id
Protein chains
313 a.a. *
FBP ×2
NAD ×2
Waters ×301
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: T and r states in the crystals of bacterial l-lactate dehydr reveal the mechanism for allosteric control
Structure: L-lactate dehydrogenase (t- and r- state tetramer chain: t, r. Engineered: yes
Source: Bifidobacterium longum subsp. Longum. Organism_taxid: 1679. Strain: subsp. Longum. Gene: bifidobacterium longum ldh gene. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.50Å     R-factor:   0.188    
Authors: S.Iwata,T.Ohta
Key ref: S.Iwata et al. (1994). T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control. Nat Struct Biol, 1, 176-185. PubMed id: 7656036
04-Jan-95     Release date:   31-Mar-95    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
E8ME30  (LDH2_BIFL2) -  L-lactate dehydrogenase 2
320 a.a.
313 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - L-lactate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-lactate + NAD+ = pyruvate + NADH
Bound ligand (Het Group name = OXM)
matches with 71.43% similarity
Bound ligand (Het Group name = NAD)
corresponds exactly
= pyruvate
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  


Nat Struct Biol 1:176-185 (1994)
PubMed id: 7656036  
T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control.
S.Iwata, K.Kamata, S.Yoshida, T.Minowa, T.Ohta.
The crystal structure of L-lactate dehydrogenase from Bifidobacterium longum, determined to 2.5 A resolution, contains a regular 1:1 complex of T- and R-state tetramers. A comparison of these two structures within the same crystal lattice and kinetical characterization of the T-R transition in solution provide an explanation for the molecular mechanism of allosteric activation. Substrate affinity is controlled by helix sliding between subunits which is triggered by the binding of the activator, fructose 1,6-bisphosphate. The proposed mechanism can explain activation by chemical modification and mutagenesis, as well as suggesting why vertebrate counterparts are not allosteric.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20356358 A.Panjkovich, and X.Daura (2010).
Assessing the structural conservation of protein pockets to study functional and allosteric sites: implications for drug discovery.
  BMC Struct Biol, 10, 9.  
20055696 J.P.Changeux (2010).
Allosteric receptors: from electric organ to cognition.
  Annu Rev Pharmacol Toxicol, 50, 1.  
19841870 Y.Duan, N.Li, C.Liu, H.Liu, Y.Cui, H.Wang, and F.Hong (2010).
Interaction between nanoparticulate anatase TiO2 and lactate dehydrogenase.
  Biol Trace Elem Res, 136, 302-313.  
19617908 J.Zhang, C.Li, T.Shi, K.Chen, X.Shen, and H.Jiang (2009).
Lys169 of human glucokinase is a determinant for glucose phosphorylation: implication for the atomic mechanism of glucokinase catalysis.
  PLoS One, 4, e6304.  
17202260 L.Fetler, E.R.Kantrowitz, and P.Vachette (2007).
Direct observation in solution of a preexisting structural equilibrium for a mutant of the allosteric aspartate transcarbamoylase.
  Proc Natl Acad Sci U S A, 104, 495-500.  
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.  
15933191 J.P.Changeux, and S.J.Edelstein (2005).
Allosteric mechanisms of signal transduction.
  Science, 308, 1424-1428.  
15016359 K.Kamata, M.Mitsuya, T.Nishimura, J.Eiki, and Y.Nagata (2004).
Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase.
  Structure, 12, 429-438.
PDB codes: 1v4s 1v4t
12644455 G.A.Grant, Z.Hu, and X.L.Xu (2003).
Hybrid tetramers reveal elements of cooperativity in Escherichia coli D-3-phosphoglycerate dehydrogenase.
  J Biol Chem, 278, 18170-18176.  
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
11331012 A.M.Grosset, B.R.Gibney, F.Rabanal, C.C.Moser, and P.L.Dutton (2001).
Proof of principle in a de novo designed protein maquette: an allosterically regulated, charge-activated conformational switch in a tetra-alpha-helix bundle.
  Biochemistry, 40, 5474-5487.  
10940245 D.S.Goodsell, and A.J.Olson (2000).
Structural symmetry and protein function.
  Annu Rev Biophys Biomol Struct, 29, 105-153.  
10712618 Y.Kawata, K.Tamura, M.Kawamura, K.Ikei, T.Mizobata, J.Nagai, M.Fujita, S.Yano, M.Tokushige, and N.Yumoto (2000).
Cloning and over-expression of thermostable Bacillus sp. YM55-1 aspartase and site-directed mutagenesis for probing a catalytic residue.
  Eur J Biochem, 267, 1847-1857.  
  10593256 S.Kumar, B.Ma, C.J.Tsai, H.Wolfson, and R.Nussinov (1999).
Folding funnels and conformational transitions via hinge-bending motions.
  Cell Biochem Biophys, 31, 141-164.  
9651527 J.P.Changeux, D.Bertrand, P.J.Corringer, S.Dehaene, S.Edelstein, C.Léna, N.Le Novère, L.Marubio, M.Picciotto, and M.Zoli (1998).
Brain nicotinic receptors: structure and regulation, role in learning and reinforcement.
  Brain Res Brain Res Rev, 26, 198-216.  
9856454 J.P.Changeux, and S.J.Edelstein (1998).
Allosteric receptors after 30 years.
  Neuron, 21, 959-980.  
9446610 S.Fushinobu, T.Ohta, and H.Matsuzawa (1998).
Homotropic activation via the subunit interaction and allosteric symmetry revealed on analysis of hybrid enzymes of L-lactate dehydrogenase.
  J Biol Chem, 273, 2971-2976.  
8994883 A.Mattevi, M.Rizzi, and M.Bolognesi (1996).
New structures of allosteric proteins revealing remarkable conformational changes.
  Curr Opin Struct Biol, 6, 824-829.  
8631972 A.Mozzarelli, S.Bettati, C.Rivetti, G.L.Rossi, G.Colotti, and E.Chiancone (1996).
Cooperative oxygen binding to scapharca inaequivalvis hemoglobin in the crystal.
  J Biol Chem, 271, 3627-3632.  
9000033 J.Stubbe, and L.N.Johnson (1996).
Catalysis and regulation.
  Curr Opin Struct Biol, 6, 733-735.  
  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.  
8810336 S.Fushinobu, K.Kamata, S.Iwata, H.Sakai, T.Ohta, and H.Matsuzawa (1996).
Allosteric activation of L-lactate dehydrogenase analyzed by hybrid enzymes with effector-sensitive and -insensitive subunits.
  J Biol Chem, 271, 25611-25616.  
8591049 A.Mattevi, G.Valentini, M.Rizzi, M.L.Speranza, M.Bolognesi, and A.Coda (1995).
Crystal structure of Escherichia coli pyruvate kinase type I: molecular basis of the allosteric transition.
  Structure, 3, 729-741.
PDB code: 1pky
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.