PDBsum entry 1e6e

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
457 a.a. *
113 a.a. *
106 a.a. *
FAD ×2
SO4 ×5
FES ×2
Waters ×274
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Adrenodoxin reductase/adrenodoxin complex of mitochondrial p450 systems
Structure: Nadph\:adrenodoxin oxidoreductase. Chain: a, c. Synonym: ar, adrenodoxin reductase, ferredoxin--NADP(+) red ferredoxin reductase, adr, adrenodoxin reductase. Engineered: yes. Other_details: covalent crosslink between lys27 of adr and adx. Adrenodoxin. Chain: b, d.
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: adrenal gland. Tissue: steroidogenic tissues. Cell: mitochondrion. Organelle: mitochondrial matrix. Cellular_location: attached to inner mitochondrial membrane.
2.30Å     R-factor:   0.222     R-free:   0.268
Authors: J.J.Mueller,A.Lapko,G.Bourenkov,K.Ruckpaul,U.Heinemann
Key ref:
J.J.Müller et al. (2001). Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis. J Biol Chem, 276, 2786-2789. PubMed id: 11053423 DOI: 10.1074/jbc.M008501200
15-Aug-00     Release date:   09-Aug-01    
Go to PROCHECK summary

Protein chains
P08165  (ADRO_BOVIN) -  NADPH:adrenodoxin oxidoreductase, mitochondrial
492 a.a.
457 a.a.
Protein chain
Pfam   ArchSchema ?
P00257  (ADX_BOVIN) -  Adrenodoxin, mitochondrial
186 a.a.
113 a.a.
Protein chain
Pfam   ArchSchema ?
P00257  (ADX_BOVIN) -  Adrenodoxin, mitochondrial
186 a.a.
106 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.  - Adrenodoxin-NADP(+) reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 reduced adrenodoxin + NADP+ = 2 oxidized adrenodoxin + NADPH
2 × reduced adrenodoxin
+ NADP(+)
= 2 × oxidized adrenodoxin
      Cofactor: FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     electron carrier activity     8 terms  


DOI no: 10.1074/jbc.M008501200 J Biol Chem 276:2786-2789 (2001)
PubMed id: 11053423  
Adrenodoxin reductase-adrenodoxin complex structure suggests electron transfer path in steroid biosynthesis.
J.J.Müller, A.Lapko, G.Bourenkov, K.Ruckpaul, U.Heinemann.
The steroid hydroxylating system of adrenal cortex mitochondria consists of the membrane-attached NADPH-dependent adrenodoxin reductase (AR), the soluble one-electron transport protein adrenodoxin (Adx), and a membrane-integrated cytochrome P450 of the CYP11 family. In the 2.3-A resolution crystal structure of the Adx.AR complex, 580 A(2) of partly polar surface are buried. Main interaction sites are centered around Asp(79), Asp(76), Asp(72), and Asp(39) of Adx and around Arg(211), Arg(240), Arg(244), and Lys(27) of AR, respectively. In particular, the region around Asp(39) defines a new protein interaction site for Adx, similar to those found in plant and bacterial ferredoxins. Additional contacts involve the electron transfer region between the redox centers of AR and Adx and C-terminal residues of Adx. The Adx residues Asp(113) to Arg(115) adopt 3(10)-helical conformation and engage in loose intermolecular contacts within a deep cleft of AR. Complex formation is accompanied by a slight domain rearrangement in AR. The [2Fe-2S] cluster of Adx and the isoalloxazine rings of FAD of AR are 10 A apart suggesting a possible electron transfer route between these redox centers. The AR.Adx complex represents the first structure of a biologically relevant complex between a ferredoxin and its reductase.
  Selected figure(s)  
Figure 1.
Fig. 1. Crystal structure of the AR·Adx complex. AR-Adx contacts occur at the primary and secondary interaction regions and the region between the [2Fe-2S] cluster of Adx and the isoalloxazine ring of the FAD of AR. C-terminal residues of Adx are also in contact with AR. The side chains of some residues involved in polar AR-Adx interactions are displayed. For close-ups of the contact sites see Figs. 3 and 4. The brown triangle marks the position of Adx Lys66 and the green marks AR Glu4, both residues maintaining another cross-link reported recently (11, 12). Figure was produced with MOLSCRIPT (17).
Figure 4.
Fig. 4. Electron transfer region between the [2Fe-2S] cluster of Adx and the FAD moiety of AR. The hypothetical electron pathway shown in red was calculated with the program HARLEM (31). Red dotted lines mark through-space electron jumps. The AR-Adx interface is stabilized by hydrogen bonds (blue dotted lines) and van der Waals contacts. Residues are labeled black for AR and red for Adx. The blue spheres are water molecules.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 2786-2789) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21536008 J.J.Müller, F.Hannemann, B.Schiffler, K.M.Ewen, R.Kappl, U.Heinemann, and R.Bernhardt (2011).
Structural and thermodynamic characterization of the adrenodoxin-like domain of the electron-transfer protein Etp1 from Schizosaccharomyces pombe.
  J Inorg Biochem, 105, 957-965.
PDB code: 2wlb
21497579 S.P.Wu, M.Bellei, S.S.Mansy, G.Battistuzzi, M.Sola, and J.A.Cowan (2011).
Redox chemistry of the Schizosaccharomyces pombe ferredoxin electron-transfer domain and influence of Cys to Ser substitutions.
  J Inorg Biochem, 105, 806-811.  
20878669 H.Komori, D.Seo, T.Sakurai, and Y.Higuchi (2010).
Crystal structure analysis of Bacillus subtilis ferredoxin-NADP(+) oxidoreductase and the structural basis for its substrate selectivity.
  Protein Sci, 19, 2279-2290.
PDB codes: 3lzw 3lzx
20033391 W.Wei, Y.Li, L.Wang, S.Liu, X.Yan, D.Mei, Y.Li, Y.Xu, P.Peng, and Q.Hu (2010).
Development of a novel Sinapis arvensis disomic addition line in Brassica napus containing the restorer gene for Nsa CMS and improved resistance to Sclerotinia sclerotiorum and pod shattering.
  Theor Appl Genet, 120, 1089-1097.  
19398961 G.P.Christophi, M.Panos, C.A.Hudson, R.L.Christophi, R.C.Gruber, A.T.Mersich, S.D.Blystone, B.Jubelt, and P.T.Massa (2009).
Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype.
  Lab Invest, 89, 742-759.  
17729269 A.May, and M.Zacharias (2008).
Energy minimization in low-frequency normal modes to efficiently allow for global flexibility during systematic protein-protein docking.
  Proteins, 70, 794-809.  
18209728 G.P.Christophi, C.A.Hudson, R.C.Gruber, C.P.Christophi, C.Mihai, L.J.Mejico, B.Jubelt, and P.T.Massa (2008).
SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients.
  Lab Invest, 88, 243-255.  
18260112 M.Medina, R.Abagyan, C.Gómez-Moreno, and J.Fernandez-Recio (2008).
Docking analysis of transient complexes: interaction of ferredoxin-NADP+ reductase with ferredoxin and flavodoxin.
  Proteins, 72, 848-862.  
18801069 Y.Kanai (2008).
Alterations of DNA methylation and clinicopathological diversity of human cancers.
  Pathol Int, 58, 544-558.  
17534532 A.W.Munro, H.M.Girvan, and K.J.McLean (2007).
Variations on a (t)heme--novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily.
  Nat Prod Rep, 24, 585-609.  
  17554177 M.Senda, S.Kishigami, S.Kimura, and T.Senda (2007).
Crystallization and preliminary X-ray analysis of the electron-transfer complex of Rieske-type [2Fe-2S] ferredoxin and NADH-dependent ferredoxin reductase derived from Acidovorax sp. strain KKS102.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 520-523.  
16941211 H.Jin, G.Tan, D.S.Brar, M.Tang, G.Li, L.Zhu, and G.He (2006).
Molecular and cytogenetic characterization of an Oryza officinalis-O. sativa chromosome 4 addition line and its progenies.
  Plant Mol Biol, 62, 769-777.  
16897340 J.D.Heaney, and S.K.Bronson (2006).
Artificial chromosome-based transgenes in the study of genome function.
  Mamm Genome, 17, 791-807.  
16329107 J.L.Chung, W.Wang, and P.E.Bourne (2006).
Exploiting sequence and structure homologs to identify protein-protein binding sites.
  Proteins, 62, 630-640.  
16581251 K.J.McLean, D.Clift, D.G.Lewis, M.Sabri, P.R.Balding, M.J.Sutcliffe, D.Leys, and A.W.Munro (2006).
The preponderance of P450s in the Mycobacterium tuberculosis genome.
  Trends Microbiol, 14, 220-228.  
16791687 Z.Y.Dong, Y.M.Wang, Z.J.Zhang, Y.Shen, X.Y.Lin, X.F.Ou, F.P.Han, and B.Liu (2006).
Extent and pattern of DNA methylation alteration in rice lines derived from introgressive hybridization of rice and Zizania latifolia Griseb.
  Theor Appl Genet, 113, 196-205.  
16038609 N.V.Strushkevich, T.N.Azeva, G.I.Lepesheva, and S.A.Usanov (2005).
Role of positively charged residues lys267, lys270, and arg411 of cytochrome p450scc (CYP11A1) in interaction with adrenodoxin.
  Biochemistry (Mosc), 70, 664-671.  
15948713 T.L.Azhikina, and E.D.Sverdlov (2005).
Study of tissue-specific CpG methylation of DNA in extended genomic loci.
  Biochemistry (Mosc), 70, 596-603.  
15948705 W.Doerfler (2005).
On the biological significance of DNA methylation.
  Biochemistry (Mosc), 70, 505-524.  
  16511100 Y.Ashikawa, Z.Fujimoto, H.Noguchi, H.Habe, T.Omori, H.Yamane, and H.Nojiri (2005).
Crystallization and preliminary X-ray diffraction analysis of the electron-transfer complex between the terminal oxygenase component and ferredoxin in the Rieske non-haem iron oxygenase system carbazole 1,9a-dioxygenase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 577-580.  
15703040 F.P.Han, Z.L.Liu, M.Tan, S.Hao, G.Fedak, and B.Liu (2004).
Mobilized retrotransposon Tos17 of rice by alien DNA introgression transposes into genes and causes structural and methylation alterations of a flanking genomic region.
  Hereditas, 141, 243-251.  
15386621 M.Prudêncio, and M.Ubbink (2004).
Transient complexes of redox proteins: structural and dynamic details from NMR studies.
  J Mol Recognit, 17, 524-539.  
15103126 N.Smith, M.Mayhew, M.J.Holden, H.Kelly, H.Robinson, A.Heroux, V.L.Vilker, and D.T.Gallagher (2004).
Structure of C73G putidaredoxin from Pseudomonas putida.
  Acta Crystallogr D Biol Crystallogr, 60, 816-822.
PDB code: 1r7s
15103624 P.B.Crowley, and M.A.Carrondo (2004).
The architecture of the binding site in redox protein complexes: implications for fast dissociation.
  Proteins, 55, 603-612.  
15340917 Y.Sargisova, F.M.Pierfederici, A.Scirè, E.Bertoli, F.Tanfani, F.Febbraio, R.Briante, Y.Karapetyan, and S.Mardanyan (2004).
Computational, spectroscopic, and resonant mirror biosensor analysis of the interaction of adrenodoxin with native and tryptophan-modified NADPH-adrenodoxin reductase.
  Proteins, 57, 302-310.  
12581212 M.Faro, B.Schiffler, A.Heinz, I.Nogués, M.Medina, R.Bernhardt, and C.Gómez-Moreno (2003).
Insights into the design of a hybrid system between Anabaena ferredoxin-NADP+ reductase and bovine adrenodoxin.
  Eur J Biochem, 270, 726-735.  
12417122 F.Seeber (2002).
Eukaryotic genomes contain a [2Fez.sbnd;2S] ferredoxin isoform with a conserved C-terminal sequence motif.
  Trends Biochem Sci, 27, 545-547.  
  11897868 P.D.Richardson, L.B.Augustin, B.T.Kren, and C.J.Steer (2002).
Gene repair and transposon-mediated gene therapy.
  Stem Cells, 20, 105-118.  
11248704 E.C.Müller, A.Lapko, A.Otto, J.J.Müller, K.Ruckpaul, and U.Heinemann (2001).
Covalently crosslinked complexes of bovine adrenodoxin with adrenodoxin reductase and cytochrome P450scc. Mass spectrometry and Edman degradation of complexes of the steroidogenic hydroxylase system.
  Eur J Biochem, 268, 1837-1843.  
11454000 G.Cauet, D.Balbuena, T.Achstetter, and B.Dumas (2001).
CYP11A1 stimulates the hydroxylase activity of CYP11B1 in mitochondria of recombinant yeast in vivo and in vitro.
  Eur J Biochem, 268, 4054-4062.  
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.