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PDBsum entry 1d4o

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Oxidoreductase PDB id
1d4o
Jmol
Contents
Protein chain
177 a.a. *
Ligands
NAP
Waters ×185
* Residue conservation analysis
PDB id:
1d4o
Name: Oxidoreductase
Title: Crystal structure of transhydrogenase domain iii at 1.2 angstroms resolution
Structure: NADP(h) transhydrogenase. Chain: a. Fragment: NADP(h) binding domain. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Cellular_location: mitochondria. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.21Å     R-factor:   0.167     R-free:   0.223
Authors: G.S.Prasad,V.Sridhar,M.Yamaguchi,Y.Hatefi,C.D.Stout
Key ref:
G.S.Prasad et al. (1999). Crystal structure of transhydrogenase domain III at 1.2 A resolution. Nat Struct Biol, 6, 1126-1131. PubMed id: 10581554 DOI: 10.1038/70067
Date:
04-Oct-99     Release date:   20-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11024  (NNTM_BOVIN) -  NAD(P) transhydrogenase, mitochondrial
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1086 a.a.
177 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: 10.1038/70067 Nat Struct Biol 6:1126-1131 (1999)
PubMed id: 10581554  
 
 
Crystal structure of transhydrogenase domain III at 1.2 A resolution.
G.S.Prasad, V.Sridhar, M.Yamaguchi, Y.Hatefi, C.D.Stout.
 
  ABSTRACT  
 
The nicotinamide nucleotide transhydrogenases (TH) of mitochondria and bacteria are membrane-intercalated proton pumps that transduce substrate binding energy and protonmotive force via protein conformational changes. In mitochondria, TH utilizes protonmotive force to promote direct hydride ion transfer from NADH to NADP, which are bound at the distinct extramembranous domains I and III, respectively. Domain II is the membrane-intercalated domain and contains the enzyme's proton channel. This paper describes the crystal structure of the NADP(H) binding domain III of bovine TH at 1.2 A resolution. The structure reveals that NADP is bound in a manner inverted from that previously observed for nucleotide binding folds. The non-classical binding mode exposes the NADP(H) nicotinamide ring for direct contact with NAD(H) in domain I, in accord with biochemical data. The surface of domain III surrounding the exposed nicotinamide is comprised of conserved residues presumed to form the interface with domain I during hydride ion transfer. Further, an adjacent region contains a number of acidic residues, forming a surface with negative electrostatic potential which may interact with extramembranous loops of domain II. Together, the distinctive surface features allow mechanistic considerations regarding the NADP(H)-promoted conformation changes that are involved in the interactions of domain III with domains I and II for hydride ion transfer and proton translocation.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Stereo view showing the details of the NADP binding site. Interactions with residues from six NADP motifs in domain III are shown, including 23 hydrogen bonds (dotted black lines), hydrophobic and stacking interactions, and short contacts to glycine residues (two conserved Gly residues, Gly 30 and Gly 165, are not shown). The NADP conformation is extended: the linked phosphates are staggered about the P-O-P bond, and both nucleotides display trans torsion angles about the ribose C4'-C5' bonds. The torsion angles about the C1'-N glycosyl bonds are syn for the nicotinamide (N7 over the ribose) and anti for adenine. The ribose pucker is C2' endo for the NMN moiety and C3' endo for the 2',5'-ADP moiety.
Figure 4.
Figure 4. a, The distribution of conserved (yellow) and semi-conserved (green) residues on the surface of domain III. The residues are colored as in Fig. 2 on the solvent accessible surface of the protein. Residues surrounding the bound NADP include those in the NADP(H) and interface motifs. The opposite view of the domain (rotated 180°) displays only one conserved or semi-conserved residue not visible in this view. It is anticipated that the surface of the protein depicted encompasses the interface formed with domain I during hydride ion transfer. The B face of the nicotinamide, which exchanges a hydride ion with the 4A position of NAD(H) in domain I, is indicated. b, The electrostatic potential of domain III plotted onto the solvent accessible surface of the protein. Eight Asp and Glu residues in the acidic patch motif ( Fig. 2) are labeled, as are Asp 108 in a NADP(H) motif, Tyr 82 in an interface motif, and Glu 129. This face of the domain is roughly orthogonal to that shown in (a) (that is, rotation of the view in (a) by 90° about the vertical axis gives the view in this figure, as can be seen by comparing the positions of Tyr 82, Glu 77 and the nicotinamide). The opposite view of the domain (rotated 180°) contains an equal number of exposed acidic and basic residues. The extensive area of negative electrostatic potential may facilitate interaction with basic residues in matrix-side loops of domain II. Also apparent in this view are the exposed 4B position of the nicotinamide, the exposed 2'-hydroxyl of the NMN ribose, and positive electrostatic potential opposite the dinucleotide phosphates.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (1999, 6, 1126-1131) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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
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
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
12230562 C.Johansson, A.Pedersen, B.G.Karlsson, and J.Rydström (2002).
Redox-sensitive loops D and E regulate NADP(H) binding in domain III and domain I-domain III interactions in proton-translocating Escherichia coli transhydrogenase.
  Eur J Biochem, 269, 4505-4515.  
11839305 L.A.Martinez-Cruz, M.K.Dreyer, D.C.Boisvert, H.Yokota, M.L.Martinez-Chantar, R.Kim, and S.H.Kim (2002).
Crystal structure of MJ1247 protein from M. jannaschii at 2.0 A resolution infers a molecular function of 3-hexulose-6-phosphate isomerase.
  Structure, 10, 195-204.
PDB code: 1jeo
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.  
11336676 J.Min, J.Landry, R.Sternglanz, and R.M.Xu (2001).
Crystal structure of a SIR2 homolog-NAD complex.
  Cell, 105, 269-279.
PDB code: 1ici
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
11027139 A.Bergkvist, C.Johansson, T.Johansson, J.Rydström, and B.G.Karlsson (2000).
Interactions of the NADP(H)-binding domain III of proton-translocating transhydrogenase from escherichia coli with NADP(H) and the NAD(H)-binding domain I studied by NMR and site-directed mutagenesis.
  Biochemistry, 39, 12595-12605.  
10839820 M.H.Saier (2000).
A functional-phylogenetic classification system for transmembrane solute transporters.
  Microbiol Mol Biol Rev, 64, 354-411.  
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.