PDBsum entry 2fbw

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
613 a.a. *
239 a.a. *
140 a.a. *
101 a.a. *
FAD ×2
TEO ×2
UNL ×95
FES ×2
SF4 ×2
F3S ×2
GOL ×4
BHG ×2
HEM ×2
CBE ×2
PEE ×2
Waters ×2000
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Avian respiratory complex ii with carboxin bound
Structure: Succinate dehydrogenase flavoprotein subunit. Chain: a, n. Succinate dehydrogenase ip subunit. Chain: b, o. Succinate dehydrogenase cytochrome b, large subun chain: c, p. Succinate dehydrogenase cytochrome b, small subun chain: d, q. Ec:
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Organism_taxid: 9031
Biol. unit: Octamer (from PQS)
2.10Å     R-factor:   0.187     R-free:   0.227
Authors: L.S.Huang,G.Sun,D.Cobessi,A.C.Wang,J.T.Shen,E.Y.Tung,V.E.And E.A.Berry
Key ref:
L.S.Huang et al. (2006). 3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme. J Biol Chem, 281, 5965-5972. PubMed id: 16371358 DOI: 10.1074/jbc.M511270200
10-Dec-05     Release date:   20-Dec-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9YHT1  (DHSA_CHICK) -  Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
665 a.a.
613 a.a.*
Protein chains
Pfam   ArchSchema ?
Q9YHT2  (DHSB_CHICK) -  Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial
290 a.a.
239 a.a.
Protein chains
Pfam   ArchSchema ?
D0VWW3  (D0VWW3_CHICK) -  Succinate dehydrogenase cytochrome b, large subunit
140 a.a.
140 a.a.*
Protein chains
Pfam   ArchSchema ?
Q5ZIS0  (DHSD_CHICK) -  Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
157 a.a.
101 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 7 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     small molecule metabolic process   6 terms 
  Biochemical function     electron carrier activity     9 terms  


DOI no: 10.1074/jbc.M511270200 J Biol Chem 281:5965-5972 (2006)
PubMed id: 16371358  
3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme.
L.S.Huang, G.Sun, D.Cobessi, A.C.Wang, J.T.Shen, E.Y.Tung, V.E.Anderson, E.A.Berry.
We report three new structures of mitochondrial respiratory Complex II (succinate ubiquinone oxidoreductase, E.C. at up to 2.1 A resolution, with various inhibitors. The structures define the conformation of the bound inhibitors and suggest the residues involved in substrate binding and catalysis at the dicarboxylate site. In particular they support the role of Arg(297) as a general base catalyst accepting a proton in the dehydrogenation of succinate. The dicarboxylate ligand in oxaloacetate-containing crystals appears to be the same as that reported for Shewanella flavocytochrome c treated with fumarate. The plant and fungal toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent adduct with the side chain of Arg(297). The modification eliminates a trypsin cleavage site in the flavoprotein, and tandem mass spectroscopic analysis of the new fragment shows the mass of Arg(297) to be increased by 83 Da and to have the potential of losing 44 Da, consistent with decarboxylation, during fragmentation.
  Selected figure(s)  
Figure 1.
FIGURE 1. Overall structure of mitochondrial complex II. The stereo ribbon diagram is colored yellow and brown (flavoprotein), green (iron protein), pink (large anchor polypeptide, chain C), and blue (small anchor peptide, chain D). The CAP domain of the flavoprotein is colored brown. The green space-filling model at the intersection between the CAP domain and the rest of the flavoprotein is the malate-like ligand, and the extended blue ball-and-stick model starting just to the right of that is the FAD cofactor. Note the first helix of anchor peptide (Chain C) packs against a helix of the IP.
Figure 4.
FIGURE 4. The dicarboxylate site in the 3-NP-treated enzyme. The density attributed to the ligand has shrunk and moved away from the flavin toward Arg^297 and His^253. It can be modeled by assuming two atoms from the backbone of 3-NP (C-3 and N) fuse with the guanidino group to form a five-membered ring, with loss of the two nitro oxygens. The carboxylate at the other end fits into the clearly forked density branching off the ring. 2F[o] - F[c] map contoured at 1.7 .
  The above figures are reprinted from an Open Access publication published by the ASBMB: J Biol Chem (2006, 281, 5965-5972) copyright 2006.  
  Figures were selected by the author.  
    Author's comment    
  These structures confirmed the role of Arg297 in ligand binding (and presumably catalysis) at the dicarboxylate active site. This had been suspected from mutagenesis and from the structure of homologous Flavocytochrome c of Shewanella, but had never been shown before in Complex II superfamily.
Structure 1YQ4 confirms the covalent binding of the plant and fungal toxin 3-nitropropionate, showing that the catalytic base arginine A297 is covalently modified. This is in contrast to a previous model from the lower-resolution structure of porcine complex II with nitropropionate bound.
-Edward Berry

Literature references that cite this PDB file's key reference

  PubMed id Reference
20938980 K.Illergård, A.Kauko, and A.Elofsson (2011).
Why are polar residues within the membrane core evolutionary conserved?
  Proteins, 79, 79-91.  
21228470 Y.Shima, Y.Ito, H.Hatabayashi, A.Koma, and K.Yabe (2011).
Five carboxin-resistant mutants exhibited various responses to carboxin and related fungicides.
  Biosci Biotechnol Biochem, 75, 181-184.  
20489732 E.Mbaya, B.Oulès, C.Caspersen, R.Tacine, H.Massinet, M.Pennuto, D.Chrétien, A.Munnich, A.Rötig, R.Rizzuto, G.A.Rutter, P.Paterlini-Bréchot, and M.Chami (2010).
Calcium signalling-dependent mitochondrial dysfunction and bioenergetics regulation in respiratory chain Complex II deficiency.
  Cell Death Differ, 17, 1855-1866.  
20000467 H.Cimen, M.J.Han, Y.Yang, Q.Tong, H.Koc, and E.C.Koc (2010).
Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria.
  Biochemistry, 49, 304-311.  
19826804 K.McLuskey, A.W.Roszak, Y.Zhu, and N.W.Isaacs (2010).
Crystal structures of all-alpha type membrane proteins.
  Eur Biophys J, 39, 723-755.  
20480544 P.Kumar, H.Kalonia, and A.Kumar (2010).
Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease.
  Behav Pharmacol, 21, 217-230.  
20693447 P.Leroux, M.Gredt, M.Leroch, and A.S.Walker (2010).
Exploring mechanisms of resistance to respiratory inhibitors in field strains of Botrytis cinerea, the causal agent of gray mold.
  Appl Environ Microbiol, 76, 6615-6630.  
19779956 S.Almeida, T.Cunha-Oliveira, M.Laço, C.R.Oliveira, and A.C.Rego (2010).
Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF.
  Neurotox Res, 17, 399-405.  
19799853 T.T.Jones, and G.J.Brewer (2010).
Age-related deficiencies in complex I endogenous substrate availability and reserve capacity of complex IV in cortical neuron electron transport.
  Biochim Biophys Acta, 1797, 167-176.  
19170876 H.D.Juhnke, H.Hiltscher, H.R.Nasiri, H.Schwalbe, and C.R.Lancaster (2009).
Production, characterization and determination of the real catalytic properties of the putative 'succinate dehydrogenase' from Wolinella succinogenes.
  Mol Microbiol, 71, 1088-1101.  
19122194 J.Morales, T.Mogi, S.Mineki, E.Takashima, R.Mineki, H.Hirawake, K.Sakamoto, S.Omura, and K.Kita (2009).
Novel mitochondrial complex II isolated from Trypanosoma cruzi is composed of 12 peptides including a heterodimeric Ip subunit.
  J Biol Chem, 284, 7255-7263.  
19710024 J.Ruprecht, V.Yankovskaya, E.Maklashina, S.Iwata, and G.Cecchini (2009).
Structure of Escherichia coli succinate:quinone oxidoreductase with an occupied and empty quinone-binding site.
  J Biol Chem, 284, 29836-29846.
PDB codes: 2wdq 2wdr 2wdv
19060309 K.Kawahara, T.Mogi, T.Q.Tanaka, M.Hata, H.Miyoshi, and K.Kita (2009).
Mitochondrial Dehydrogenases in the Aerobic Respiratory Chain of the Rodent Malaria Parasite Plasmodium yoelii yoelii.
  J Biochem, 145, 229-237.  
19480389 L.Hedstrom (2009).
IMP dehydrogenase: structure, mechanism, and inhibition.
  Chem Rev, 109, 2903-2928.  
19634179 N.Brunet, O.Tarabal, J.E.Esquerda, and J.Calderó (2009).
Excitotoxic motoneuron degeneration induced by glutamate receptor agonists and mitochondrial toxins in organotypic cultures of chick embryo spinal cord.
  J Comp Neurol, 516, 277-290.  
19627208 P.Kumar, and A.Kumar (2009).
Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington's disease.
  J Med Food, 12, 591-600.  
19682208 R.Lagoa, C.Lopez-Sanchez, A.K.Samhan-Arias, C.M.Gañan, V.Garcia-Martinez, and C.Gutierrez-Merino (2009).
Kaempferol protects against rat striatal degeneration induced by 3-nitropropionic acid.
  J Neurochem, 111, 473-487.  
19192292 R.M.Gawryluk, and M.W.Gray (2009).
A split and rearranged nuclear gene encoding the iron-sulfur subunit of mitochondrial succinate dehydrogenase in Euglenozoa.
  BMC Res Notes, 2, 16.  
18418633 E.A.Berry, and F.A.Walker (2008).
Bis-histidine-coordinated hemes in four-helix bundles: how the geometry of the bundle controls the axial imidazole plane orientations in transmembrane cytochromes of mitochondrial complexes II and III and related proteins.
  J Biol Inorg Chem, 13, 481-498.  
18296637 J.I.Yeh, U.Chinte, and S.Du (2008).
Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism.
  Proc Natl Acad Sci U S A, 105, 3280-3285.
PDB codes: 2qcu 2r45 2r46 2r4e 2r4j
18547066 K.Ikehata, T.G.Duzhak, N.A.Galeva, T.Ji, Y.M.Koen, and R.P.Hanzlik (2008).
Protein targets of reactive metabolites of thiobenzamide in rat liver in vivo.
  Chem Res Toxicol, 21, 1432-1442.  
18372923 L.F.Dong, P.Low, J.C.Dyason, X.F.Wang, L.Prochazka, P.K.Witting, R.Freeman, E.Swettenham, K.Valis, J.Liu, R.Zobalova, J.Turanek, D.R.Spitz, F.E.Domann, I.E.Scheffler, S.J.Ralph, and J.Neuzil (2008).
Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II.
  Oncogene, 27, 4324-4335.  
18536726 M.Jormakka, K.Yokoyama, T.Yano, M.Tamakoshi, S.Akimoto, T.Shimamura, P.Curmi, and S.Iwata (2008).
Molecular mechanism of energy conservation in polysulfide respiration.
  Nat Struct Mol Biol, 15, 730-737.
PDB codes: 2vpw 2vpx 2vpy 2vpz
18385138 T.M.Tomasiak, E.Maklashina, G.Cecchini, and T.M.Iverson (2008).
A threonine on the active site loop controls transition state formation in Escherichia coli respiratory complex II.
  J Biol Chem, 283, 15460-15468.
PDB code: 3cir
17376234 B.E.Baysal, E.C.Lawrence, and R.E.Ferrell (2007).
Sequence variation in human succinate dehydrogenase genes: evidence for long-term balancing selection on SDHA.
  BMC Biol, 5, 12.  
17429617 K.Xiong, H.Cai, X.G.Luo, R.G.Struble, R.W.Clough, and X.X.Yan (2007).
Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina.
  Exp Brain Res, 181, 435-446.  
17989224 Q.M.Tran, R.A.Rothery, E.Maklashina, G.Cecchini, and J.H.Weiner (2007).
Escherichia coli succinate dehydrogenase variant lacking the heme b.
  Proc Natl Acad Sci U S A, 104, 18007-18012.  
18005427 S.L.Cole, and R.Vassar (2007).
The Alzheimer's disease beta-secretase enzyme, BACE1.
  Mol Neurodegener, 2, 22.  
17011837 A.Bacsi, M.Woodberry, W.Widger, J.Papaconstantinou, S.Mitra, J.W.Peterson, and I.Boldogh (2006).
Localization of superoxide anion production to mitochondrial electron transport chain in 3-NPA-treated cells.
  Mitochondrion, 6, 235-244.  
17050691 J.Zhang, F.E.Frerman, and J.J.Kim (2006).
Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool.
  Proc Natl Acad Sci U S A, 103, 16212-16217.
PDB codes: 2gmh 2gmj
16935256 L.S.Huang, J.T.Shen, A.C.Wang, and E.A.Berry (2006).
Crystallographic studies of the binding of ligands to the dicarboxylate site of Complex II, and the identity of the ligand in the "oxaloacetate-inhibited" state.
  Biochim Biophys Acta, 1757, 1073-1083.
PDB codes: 2h88 2h89
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.