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PDBsum entry 1djl

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Oxidoreductase PDB id
1djl
Jmol
Contents
Protein chain
182 a.a. *
Ligands
SO4 ×2
NAP ×2
GOL ×2
Waters ×80
* Residue conservation analysis
PDB id:
1djl
Name: Oxidoreductase
Title: The crystal structure of human transhydrogenase domain iii w NADP
Structure: Transhydrogenase diii. Chain: a, b. Fragment: residues 837-1086. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.237     R-free:   0.258
Authors: S.A.White,S.J.Peak,N.P.Cotton,J.B.Jackson
Key ref:
S.A.White et al. (2000). The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria. Structure, 8, 1. PubMed id: 10673423 DOI: 10.1016/S0969-2126(00)00075-7
Date:
03-Dec-99     Release date:   06-Dec-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q13423  (NNTM_HUMAN) -  NAD(P) transhydrogenase, mitochondrial
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1086 a.a.
182 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.6.1.2  - NAD(P)(+) transhydrogenase (Re/Si-specific).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NADPH + NAD+ = NADP+ + NADH
NADPH
Bound ligand (Het Group name = NAP)
corresponds exactly
+ NAD(+)
= NADP(+)
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     NADP binding     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(00)00075-7 Structure 8:1 (2000)
PubMed id: 10673423  
 
 
The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria.
S.A.White, S.J.Peake, S.McSweeney, G.Leonard, N.P.Cotton, J.B.Jackson.
 
  ABSTRACT  
 
BACKGROUND: Transhydrogenase, located in the inner membranes of animal mitochondria and the cytoplasmic membranes of bacteria, couples the transfer of reducing equivalents between NAD(H) and NADP(H) to proton pumping. The protein comprises three subunits termed dI, dII and dIII. The dII component spans the membrane. The dI component, which contains the binding site for NAD(+)/NADH, and the dIII component, which has the binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping is probably coupled to changes in the binding affinities of dIII for NADP(+) and NADPH. RESULTS: The first X-ray structure of the NADP(H)-binding component, dIII, of human heart transhydrogenase is described here at 2.0 A resolution. It comprises a single domain resembling the classical Rossmann fold, but NADP(+) binds to dIII with a reversed orientation. The first betaalphabetaalphabeta motif of dIII contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different function to that in the classical Rossmann structure. The nicotinamide ring of NADP(+) is located on a ridge where it is exposed to interaction with NADH on the dI subunit. Two distinctive features of the dIII structure are helix D/loop D, which projects from the beta sheet, and loop E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D interacts with the bound nucleotide and loop E, and probably interacts with the membrane-spanning dII. Changes in ionisation and conformation in helix D/loop D, resulting from proton translocation through dII, are thought to be responsible for the changes in affinity of dIII for NADP(+) and NADPH that drive the reaction.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. The NADP+-binding pocket of dIII. Amino acid residues are shown with atoms in standard colours: C, yellow; O, red; and N, blue. The nucleotide is shown in red. NIC, nicotinamide ring; ADE, adenine ring.
 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1-0) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21460451 N.S.Pannu, W.J.Waterreus, P.Skubák, I.Sikharulidze, J.P.Abrahams, and R.A.de Graaff (2011).
Recent advances in the CRANK software suite for experimental phasing.
  Acta Crystallogr D Biol Crystallogr, 67, 331-337.  
20606258 P.Skubák, W.J.Waterreus, and N.S.Pannu (2010).
Multivariate phase combination improves automated crystallographic model building.
  Acta Crystallogr D Biol Crystallogr, 66, 783-788.  
18972197 A.Pedersen, G.B.Karlsson, and J.Rydström (2008).
Proton-translocating transhydrogenase: an update of unsolved and controversial issues.
  J Bioenerg Biomembr, 40, 463-473.  
18560156 J.Marienhagen, T.Sandalova, H.Sahm, L.Eggeling, and G.Schneider (2008).
Insights into the structural basis of substrate recognition by histidinol-phosphate aminotransferase from Corynebacterium glutamicum.
  Acta Crystallogr D Biol Crystallogr, 64, 675-685.
PDB codes: 3cq4 3cq5 3cq6
18093968 O.M.Ganichkin, X.M.Xu, B.A.Carlson, H.Mix, D.L.Hatfield, V.N.Gladyshev, and M.C.Wahl (2008).
Structure and catalytic mechanism of eukaryotic selenocysteine synthase.
  J Biol Chem, 283, 5849-5865.
PDB codes: 3bc8 3bca 3bcb
16533815 T.H.Brondijk, G.I.van Boxel, O.C.Mather, P.G.Quirk, S.A.White, and J.B.Jackson (2006).
The role of invariant amino acid residues at the hydride transfer site of proton-translocating transhydrogenase.
  J Biol Chem, 281, 13345-13354.
PDB codes: 2fr8 2frd 2fsv
16301796 P.Skubák, S.Ness, and N.S.Pannu (2005).
Extending the resolution and phase-quality limits in automated model building with iterative refinement.
  Acta Crystallogr D Biol Crystallogr, 61, 1626-1635.  
15498941 A.Paiardini, F.Bossa, and S.Pascarella (2004).
Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
  Protein Sci, 13, 2992-3005.  
15039572 C.Oswald, T.Johansson, S.Törnroth, M.Okvist, and U.Krengel (2004).
Crystallization and preliminary crystallographic analysis of the NAD(H)-binding domain of Escherichia coli transhydrogenase.
  Acta Crystallogr D Biol Crystallogr, 60, 743-745.  
12791694 A.Singh, J.D.Venning, P.G.Quirk, G.I.van Boxel, D.J.Rodrigues, S.A.White, and J.B.Jackson (2003).
Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation.
  J Biol Chem, 278, 33208-33216.
PDB codes: 1pt9 1ptj
12972415 J.Broos, E.Gabellieri, G.I.van Boxel, J.B.Jackson, and G.B.Strambini (2003).
Tryptophan phosphorescence spectroscopy reveals that a domain in the NAD(H)-binding component (dI) of transhydrogenase from Rhodospirillum rubrum has an extremely rigid and conformationally homogeneous protein core.
  J Biol Chem, 278, 47578-47584.  
12952962 M.Yamaguchi, and C.D.Stout (2003).
Essential glycine in the proton channel of Escherichia coli transhydrogenase.
  J Biol Chem, 278, 45333-45339.  
14567675 V.Sundaresan, M.Yamaguchi, J.Chartron, and C.D.Stout (2003).
Conformational change in the NADP(H) binding domain of transhydrogenase defines four states.
  Biochemistry, 42, 12143-12153.
PDB codes: 1pno 1pnq
12218056 J.Sandmark, S.Mann, A.Marquet, and G.Schneider (2002).
Structural basis for the inhibition of the biosynthesis of biotin by the antibiotic amiclenomycin.
  J Biol Chem, 277, 43352-43358.
PDB codes: 1mly 1mlz
12087099 M.Yamaguchi, C.D.Stout, and Y.Hatefi (2002).
The proton channel of the energy-transducing nicotinamide nucleotide transhydrogenase of Escherichia coli.
  J Biol Chem, 277, 33670-33675.  
11231296 D.J.Rodrigues, J.D.Venning, P.G.Quirk, and J.B.Jackson (2001).
A change in ionization of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase regulates both hydride transfer and nucleotide release.
  Eur J Biochem, 268, 1430-1438.  
11250201 N.P.Cotton, S.A.White, S.J.Peake, S.McSweeney, and J.B.Jackson (2001).
The crystal structure of an asymmetric complex of the two nucleotide binding components of proton-translocating transhydrogenase.
  Structure, 9, 165-176.
PDB code: 1hzz
10997900 P.A.Buckley, J.Baz Jackson, T.Schneider, S.A.White, D.W.Rice, and P.J.Baker (2000).
Protein-protein recognition, hydride transfer and proton pumping in the transhydrogenase complex.
  Structure, 8, 809-815.
PDB code: 1f8g
11004441 T.Bizouarn, J.Meuller, M.Axelsson, and J.Rydström (2000).
The transmembrane domain and the proton channel in proton-pumping transhydrogenases.
  Biochim Biophys Acta, 1459, 284-290.  
10773166 T.Bizouarn, O.Fjellström, J.Meuller, M.Axelsson, A.Bergkvist, C.Johansson, B.Göran Karlsson, and J.Rydström (2000).
Proton translocating nicotinamide nucleotide transhydrogenase from E. coli. Mechanism of action deduced from its structural and catalytic properties.
  Biochim Biophys Acta, 1457, 211-228.  
10824114 T.Bizouarn, O.Fjellström, M.Axelsson, T.V.Korneenko, N.B.Pestov, M.V.Ivanova, M.V.Egorov, M.Shakhparonov, and J.Rydström (2000).
Interactions between the soluble domain I of nicotinamide nucleotide transhydrogenase from Rhodospirillum rubrum and transhydrogenase from Escherichia coli. Effects on catalytic and H+-pumping activities.
  Eur J Biochem, 267, 3281-3288.  
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.