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PDBsum entry 1nu1

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1nu1
Jmol
Contents
Protein chains
446 a.a. *
423 a.a. *
378 a.a. *
241 a.a. *
196 a.a. *
105 a.a. *
75 a.a. *
70 a.a. *
57 a.a. *
61 a.a. *
53 a.a. *
Ligands
HEM ×3
FES
QNO
Waters ×2
* Residue conservation analysis
PDB id:
1nu1
Name: Oxidoreductase
Title: Crystal structure of mitochondrial cytochrome bc1 complexed nonyl-4-hydroxyquinoline n-oxide (nqno)
Structure: Ubiquinol-cytochromE C reductase complex core pro mitochondrial. Chain: a. Ubiquinol-cytochromE C reductase complex core pro mitochondrial. Chain: b. Synonym: complex iii subunit ii. Cytochrome b. Chain: c.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organism_taxid: 9913
Biol. unit: 22mer (from PDB file)
Resolution:
3.20Å     R-factor:   0.217     R-free:   0.296
Authors: X.Gao,X.Wen,L.Esser,B.Quinn,L.Yu,C.-A.Yu,D.Xia
Key ref:
X.Gao et al. (2003). Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site. Biochemistry, 42, 9067-9080. PubMed id: 12885240 DOI: 10.1021/bi0341814
Date:
30-Jan-03     Release date:   07-Oct-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31800  (QCR1_BOVIN) -  Cytochrome b-c1 complex subunit 1, mitochondrial
Seq:
Struc:
480 a.a.
446 a.a.
Protein chain
Pfam   ArchSchema ?
P23004  (QCR2_BOVIN) -  Cytochrome b-c1 complex subunit 2, mitochondrial
Seq:
Struc:
453 a.a.
423 a.a.
Protein chain
Pfam   ArchSchema ?
P00157  (CYB_BOVIN) -  Cytochrome b
Seq:
Struc:
379 a.a.
378 a.a.
Protein chain
Pfam   ArchSchema ?
P00125  (CY1_BOVIN) -  Cytochrome c1, heme protein, mitochondrial
Seq:
Struc:
325 a.a.
241 a.a.
Protein chain
Pfam   ArchSchema ?
P13272  (UCRI_BOVIN) -  Cytochrome b-c1 complex subunit Rieske, mitochondrial
Seq:
Struc:
274 a.a.
196 a.a.
Protein chain
Pfam   ArchSchema ?
P00129  (QCR7_BOVIN) -  Cytochrome b-c1 complex subunit 7
Seq:
Struc:
111 a.a.
105 a.a.*
Protein chain
Pfam   ArchSchema ?
P13271  (QCR8_BOVIN) -  Cytochrome b-c1 complex subunit 8
Seq:
Struc:
82 a.a.
75 a.a.
Protein chain
Pfam   ArchSchema ?
P00126  (QCR6_BOVIN) -  Cytochrome b-c1 complex subunit 6, mitochondrial
Seq:
Struc:
91 a.a.
70 a.a.
Protein chain
Pfam   ArchSchema ?
P13272  (UCRI_BOVIN) -  Cytochrome b-c1 complex subunit Rieske, mitochondrial
Seq:
Struc:
274 a.a.
57 a.a.
Protein chain
Pfam   ArchSchema ?
P00130  (QCR9_BOVIN) -  Cytochrome b-c1 complex subunit 9
Seq:
Struc:
64 a.a.
61 a.a.
Protein chain
Pfam   ArchSchema ?
P07552  (QCR10_BOVIN) -  Cytochrome b-c1 complex subunit 10
Seq:
Struc:
56 a.a.
53 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains E, I: E.C.1.10.2.2  - Quinol--cytochrome-c reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Quinol + 2 ferricytochrome c = quinone + 2 ferrocytochrome c + 2 H+
Quinol
Bound ligand (Het Group name = QNO)
matches with 57.14% similarity
+
2 × ferricytochrome c
Bound ligand (Het Group name = HEM)
matches with 63.64% similarity
= quinone
+ 2 × ferrocytochrome c
+ 2 × H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   8 terms 
  Biological process     oxidation-reduction process   13 terms 
  Biochemical function     catalytic activity     10 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/bi0341814 Biochemistry 42:9067-9080 (2003)
PubMed id: 12885240  
 
 
Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site.
X.Gao, X.Wen, L.Esser, B.Quinn, L.Yu, C.A.Yu, D.Xia.
 
  ABSTRACT  
 
Cytochrome bc(1) is an integral membrane protein complex essential to cellular respiration and photosynthesis. The Q cycle reaction mechanism of bc(1) postulates a separated quinone reduction (Q(i)) and quinol oxidation (Q(o)) site. In a complete catalytic cycle, a quinone molecule at the Q(i) site receives two electrons from the b(H) heme and two protons from the negative side of the membrane; this process is specifically inhibited by antimycin A and NQNO. The structures of bovine mitochondrial bc(1) in the presence or absence of bound substrate ubiquinone and with either the bound antimycin A(1) or NQNO were determined and refined. A ubiquinone with its first two isoprenoid repeats and an antimycin A(1) were identified in the Q(i) pocket of the substrate and inhibitor bound structures, respectively; the NQNO, on the other hand, was identified in both Q(i) and Q(o) pockets in the inhibitor complex. The two inhibitors occupied different portions of the Q(i) pocket and competed with substrate for binding. In the Q(o) pocket, the NQNO behaves similarly to stigmatellin, inducing an iron-sulfur protein conformational arrest. Extensive binding interactions and conformational adjustments of residues lining the Q(i) pocket provide a structural basis for the high affinity binding of antimycin A and for phenotypes of inhibitor resistance. A two-water-mediated ubiquinone protonation mechanism is proposed involving three Q(i) site residues His(201), Lys(227), and Asp(228).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21112412 A.Gómez-Durán, D.Pacheu-Grau, M.J.López-Pérez, J.Montoya, and E.Ruiz-Pesini (2011).
Mitochondrial pharma-Q-genomics: targeting the OXPHOS cytochrome b.
  Drug Discov Today, 16, 176-180.  
20025846 E.A.Berry, L.S.Huang, D.W.Lee, F.Daldal, K.Nagai, and N.Minagawa (2010).
Ascochlorin is a novel, specific inhibitor of the mitochondrial cytochrome bc1 complex.
  Biochim Biophys Acta, 1797, 360-370.
PDB code: 3h1l
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.  
19219048 A.Guskov, J.Kern, A.Gabdulkhakov, M.Broser, A.Zouni, and W.Saenger (2009).
Cyanobacterial photosystem II at 2.9-A resolution and the role of quinones, lipids, channels and chloride.
  Nat Struct Mol Biol, 16, 334-342.
PDB codes: 3bz1 3bz2
19415898 M.Sarewicz, M.Dutka, W.Froncisz, and A.Osyczka (2009).
Magnetic interactions sense changes in distance between heme b(L) and the iron-sulfur cluster in cytochrome bc(1).
  Biochemistry, 48, 5708-5720.  
  19774111 Q.L.Chen, X.S.Tang, W.J.Yao, and S.Q.Lu (2009).
Bioinformatics analysis of the complete sequences of cytochrome b of Takydromus sylvaticus and modeling the tertiary structure of encoded protein.
  Int J Biol Sci, 5, 596-602.  
19175316 R.E.Berry, M.N.Shokhirev, A.Y.Ho, F.Yang, T.K.Shokhireva, H.Zhang, A.Weichsel, W.R.Montfort, and F.A.Walker (2009).
Effect of mutation of carboxyl side-chain amino acids near the heme on the midpoint potentials and ligand binding constants of nitrophorin 2 and its NO, histamine, and imidazole complexes.
  J Am Chem Soc, 131, 2313-2327.
PDB code: 3fll
19503808 W.A.Beckstead, M.T.Ebbert, M.J.Rowe, and D.A.McClellan (2009).
Evolutionary pressure on mitochondrial cytochrome b is consistent with a role of CytbI7T affecting longevity during caloric restriction.
  PLoS One, 4, e5836.  
18766386 Y.El Khoury, and P.Hellwig (2009).
Infrared spectroscopic characterization of copper-polyhistidine from 1,800 to 50 cm(-1): model systems for copper coordination.
  J Biol Inorg Chem, 14, 23-34.  
18501698 A.R.Crofts, J.T.Holland, D.Victoria, D.R.Kolling, S.A.Dikanov, R.Gilbreth, S.Lhee, R.Kuras, and M.G.Kuras (2008).
The Q-cycle reviewed: How well does a monomeric mechanism of the bc(1) complex account for the function of a dimeric complex?
  Biochim Biophys Acta, 1777, 1001-1019.  
18701458 B.Gurung, L.Yu, and C.A.Yu (2008).
Stigmatellin Induces Reduction of Iron-Sulfur Protein in the Oxidized Cytochrome bc1 Complex.
  J Biol Chem, 283, 28087-28094.  
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.  
18022381 F.A.Rotsaert, M.G.Ding, and B.L.Trumpower (2008).
Differential efficacy of inhibition of mitochondrial and bacterial cytochrome bc1 complexes by center N inhibitors antimycin, ilicicolin H and funiculosin.
  Biochim Biophys Acta, 1777, 211-219.  
18039651 L.Esser, M.Elberry, F.Zhou, C.A.Yu, L.Yu, and D.Xia (2008).
Inhibitor-complexed Structures of the Cytochrome bc1 from the Photosynthetic Bacterium Rhodobacter sphaeroides.
  J Biol Chem, 283, 2846-2857.
PDB codes: 2qjk 2qjp 2qjy
18996700 P.J.Crowley, E.A.Berry, T.Cromartie, F.Daldal, C.R.Godfrey, D.W.Lee, J.E.Phillips, A.Taylor, and R.Viner (2008).
The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.
  Bioorg Med Chem, 16, 10345-10355.
PDB code: 3cwb
18471987 R.Covian, and B.L.Trumpower (2008).
Regulatory interactions in the dimeric cytochrome bc(1) complex: the advantages of being a twin.
  Biochim Biophys Acta, 1777, 1079-1091.  
18956237 S.E.Chobot, H.Zhang, C.C.Moser, and P.L.Dutton (2008).
Breaking the Q-cycle: finding new ways to study Qo through thermodynamic manipulations.
  J Bioenerg Biomembr, 40, 501-507.  
18852042 T.A.Theodossiou, A.Papakyriakou, and J.S.Hothersall (2008).
Molecular modeling and experimental evidence for hypericin as a substrate for mitochondrial complex III; mitochondrial photodamage as demonstrated using specific inhibitors.
  Free Radic Biol Med, 45, 1581-1590.  
17369262 A.M.James, M.S.Sharpley, A.R.Manas, F.E.Frerman, J.Hirst, R.A.Smith, and M.P.Murphy (2007).
Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases.
  J Biol Chem, 282, 14708-14718.  
17200733 A.Y.Mulkidjanian (2007).
Proton translocation by the cytochrome bc1 complexes of phototrophic bacteria: introducing the activated Q-cycle.
  Photochem Photobiol Sci, 6, 19-34.  
17457691 D.Xia, L.Esser, L.Yu, and C.A.Yu (2007).
Structural basis for the mechanism of electron bifurcation at the quinol oxidation site of the cytochrome bc1 complex.
  Photosynth Res, 92, 17-34.  
17498743 E.Yamashita, H.Zhang, and W.A.Cramer (2007).
Structure of the cytochrome b6f complex: quinone analogue inhibitors as ligands of heme cn.
  J Mol Biol, 370, 39-52.
PDB codes: 2e74 2e75 2e76
17360398 J.Zhu, T.Egawa, S.R.Yeh, L.Yu, and C.A.Yu (2007).
Simultaneous reduction of iron-sulfur protein and cytochrome b(L) during ubiquinol oxidation in cytochrome bc(1) complex.
  Proc Natl Acad Sci U S A, 104, 4864-4869.  
17573435 L.Giachini, F.Francia, G.Veronesi, D.W.Lee, F.Daldal, L.S.Huang, E.A.Berry, T.Cocco, S.Papa, F.Boscherini, and G.Venturoli (2007).
X-Ray absorption studies of Zn2+ binding sites in bacterial, avian, and bovine cytochrome bc1 complexes.
  Biophys J, 93, 2934-2951.  
17616531 S.A.Dikanov, J.T.Holland, B.Endeward, D.R.Kolling, R.I.Samoilova, T.F.Prisner, and A.R.Crofts (2007).
Hydrogen bonds between nitrogen donors and the semiquinone in the Qi-site of the bc1 complex.
  J Biol Chem, 282, 25831-25841.  
17213201 S.B.Le, M.K.Hailer, S.Buhrow, Q.Wang, K.Flatten, P.Pediaditakis, K.C.Bible, L.D.Lewis, E.A.Sausville, Y.P.Pang, M.M.Ames, J.J.Lemasters, E.L.Holmuhamedov, and S.H.Kaufmann (2007).
Inhibition of mitochondrial respiration as a source of adaphostin-induced reactive oxygen species and cytotoxicity.
  J Biol Chem, 282, 8860-8872.  
16829675 E.Maklashina, P.Hellwig, R.A.Rothery, V.Kotlyar, Y.Sher, J.H.Weiner, and G.Cecchini (2006).
Differences in protonation of ubiquinone and menaquinone in fumarate reductase from Escherichia coli.
  J Biol Chem, 281, 26655-26664.  
16586113 F.A.Walker (2006).
The heme environment of mouse neuroglobin: histidine imidazole plane orientations obtained from solution NMR and EPR spectroscopy as compared with X-ray crystallography.
  J Biol Inorg Chem, 11, 391-397.  
16671046 H.B.Yi, M.Diefenbach, Y.C.Choi, E.C.Lee, H.M.Lee, B.H.Hong, and K.S.Kim (2006).
Interactions of neutral and cationic transition metals with the redox system of hydroquinone and quinone: theoretical characterization of the binding topologies, and implications for the formation of nanomaterials.
  Chemistry, 12, 4885-4892.  
16371475 J.Yan, G.Kurisu, and W.A.Cramer (2006).
Intraprotein transfer of the quinone analogue inhibitor 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone in the cytochrome b6f complex.
  Proc Natl Acad Sci U S A, 103, 69-74.
PDB code: 2d2c
16924113 L.Esser, X.Gong, S.Yang, L.Yu, C.A.Yu, and D.Xia (2006).
Surface-modulated motion switch: capture and release of iron-sulfur protein in the cytochrome bc1 complex.
  Proc Natl Acad Sci U S A, 103, 13045-13050.
PDB codes: 2fyn 2fyu
16987808 M.G.Ding, J.P.di Rago, and B.L.Trumpower (2006).
Investigating the Qn site of the cytochrome bc1 complex in Saccharomyces cerevisiae with mutants resistant to ilicicolin H, a novel Qn site inhibitor.
  J Biol Chem, 281, 36036-36043.  
16825195 S.Chatterjee, P.Home, S.Mukherjee, B.Mahata, S.Goswami, G.Dhar, and S.Adhya (2006).
An RNA-binding respiratory component mediates import of type II tRNAs into Leishmania mitochondria.
  J Biol Chem, 281, 25270-25277.  
16433558 T.Teschner, L.Yatsunyk, V.Schünemann, H.Paulsen, H.Winkler, C.Hu, W.R.Scheidt, F.A.Walker, and A.X.Trautwein (2006).
Models of the membrane-bound cytochromes: mössbauer spectra of crystalline low-spin ferriheme complexes having axial ligand plane dihedral angles ranging from 0 degree to 90 degrees.
  J Am Chem Soc, 128, 1379-1389.  
16756511 W.A.Cramer, H.Zhang, J.Yan, G.Kurisu, and J.L.Smith (2006).
Transmembrane traffic in the cytochrome b6f complex.
  Annu Rev Biochem, 75, 769-790.  
15788391 A.M.James, H.M.Cochemé, R.A.Smith, and M.P.Murphy (2005).
Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. Implications for the use of exogenous ubiquinones as therapies and experimental tools.
  J Biol Chem, 280, 21295-21312.  
15878858 B.Gurung, L.Yu, D.Xia, and C.A.Yu (2005).
The iron-sulfur cluster of the Rieske iron-sulfur protein functions as a proton-exiting gate in the cytochrome bc(1) complex.
  J Biol Chem, 280, 24895-24902.  
16060661 J.W.Cooley, T.Ohnishi, and F.Daldal (2005).
Binding dynamics at the quinone reduction (Qi) site influence the equilibrium interactions of the iron sulfur protein and hydroquinone oxidation (Qo) site of the cytochrome bc1 complex.
  Biochemistry, 44, 10520-10532.  
16024040 L.S.Huang, D.Cobessi, E.Y.Tung, and E.A.Berry (2005).
Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern.
  J Mol Biol, 351, 573-597.
PDB codes: 1pp9 1ppj 2a06
15632120 M.E.Nelson, G.Finazzi, Q.J.Wang, K.A.Middleton-Zarka, J.Whitmarsh, and T.Kallas (2005).
Cytochrome b6 arginine 214 of Synechococcus sp. PCC 7002, a key residue for quinone-reductase site function and turnover of the cytochrome bf complex.
  J Biol Chem, 280, 10395-10402.  
14977419 A.R.Crofts (2004).
The cytochrome bc1 complex: function in the context of structure.
  Annu Rev Physiol, 66, 689-733.  
15313237 J.L.Smith, H.Zhang, J.Yan, G.Kurisu, and W.A.Cramer (2004).
Cytochrome bc complexes: a common core of structure and function surrounded by diversity in the outlying provinces.
  Curr Opin Struct Biol, 14, 432-439.  
14736869 S.A.Dikanov, R.I.Samoilova, D.R.Kolling, J.T.Holland, and A.R.Crofts (2004).
Hydrogen bonds involved in binding the Qi-site semiquinone in the bc1 complex, identified through deuterium exchange using pulsed EPR.
  J Biol Chem, 279, 15814-15823.  
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.