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PDBsum entry 1sqq

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1sqq
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. *
59 a.a. *
54 a.a. *
Ligands
HEM ×3
UQ2
OST
FES
Waters ×182
* Residue conservation analysis
PDB id:
1sqq
Name: Oxidoreductase
Title: Crystal structure analysis of bovine bc1 with methoxy acryla stilbene (moas)
Structure: Ubiquinol-cytochromE-C reductase complex core pro mitochondrial precursor. Chain: a. Fragment: core protein 1. Ubiquinol-cytochromE-C reductase complex core pro mitochondrial precursor. Chain: b. Fragment: core protein 2. Synonym: complex iii subunit ii.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organism_taxid: 9913
Biol. unit: 22mer (from PDB file)
Resolution:
3.00Å     R-factor:   0.230     R-free:   0.295
Authors: L.Esser,B.Quinn,Y.F.Li,M.Zhang,M.Elberry,L.Yu,C.A.Yu,D.Xia
Key ref:
L.Esser et al. (2004). Crystallographic studies of quinol oxidation site inhibitors: a modified classification of inhibitors for the cytochrome bc(1) complex. J Mol Biol, 341, 281-302. PubMed id: 15312779 DOI: 10.1016/j.jmb.2004.05.065
Date:
19-Mar-04     Release date:   25-Oct-05    
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.
59 a.a.
Protein chain
Pfam   ArchSchema ?
P07552  (QCR10_BOVIN) -  Cytochrome b-c1 complex subunit 10
Seq:
Struc:
56 a.a.
54 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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 = UQ2)
corresponds exactly
+
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  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2004.05.065 J Mol Biol 341:281-302 (2004)
PubMed id: 15312779  
 
 
Crystallographic studies of quinol oxidation site inhibitors: a modified classification of inhibitors for the cytochrome bc(1) complex.
L.Esser, B.Quinn, Y.F.Li, M.Zhang, M.Elberry, L.Yu, C.A.Yu, D.Xia.
 
  ABSTRACT  
 
Cytochrome bc(1) is an integral membrane protein complex essential for cellular respiration and photosynthesis; it couples electron transfer from quinol to cytochrome c to proton translocation across the membrane. Specific bc(1) inhibitors have not only played crucial roles in elucidating the mechanism of bc(1) function but have also provided leads for the development of novel antibiotics. Crystal structures of bovine bc(1) in complex with the specific Q(o) site inhibitors azoxystrobin, MOAS, myxothiazol, stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole were determined. Interactions, conformational changes and possible mechanisms of resistance, specific to each inhibitor, were defined. Residues and secondary structure elements that are capable of discriminating different classes of Q(o) site inhibitors were identified for the cytochrome b subunit. Directions in the displacement of the cd1 helix of cytochrome b subunit in response to various Q(o) site inhibitors were correlated to the binary conformational switch of the extrinsic domain of the iron-sulfur protein subunit. The new structural information, together with structures previously determined, provide a basis that, combined with biophysical and mutational data, suggest a modification to the existing classification of bc(1) inhibitors. bc(1) inhibitors are grouped into three classes: class P inhibitors bind to the Q(o) site, class N inhibitors bind to the Q(i) site and the class PN inhibitors target both sites. Class P contains two subgroups, Pm and Pf, that are distinct by their ability to induce mobile or fixed conformation of iron-sulfur protein.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Structures of cyt b and ISP subunit in the bc[1] complex. A, Ribbon diagram of the dimeric cyt b and ISP in the bc[1] complex. Two cyt b subunits (labeled cyt b in light blue and cyt b-sym in green, respectively) and two ISP subunits (labeled ISP in yellow and ISP-sym in red, respectively) related by a molecular 2-fold symmetry are shown. The eight TM helices of cyt b are named sequentially from A to H. The two b-type hemes labeled b[L] and b[H] are shown as the ball-and-stick models. Two active sites in the cyt b are labeled: one is the quinone reduction site (Q[i]) and the other is the quinol oxidation site (Q[o]). The surface depression in cyt b on the inter-membrane space (IMS) side is labeled as the ISP-docking crater for interacting with the ISP. B, Stereo pair: structural environment of the native Q[o] site. The Q[o] pocket is depicted as a GRASP[64.] surface with the surrounding secondary structure elements. Helices cd1, cd2, and ef as well as parts of C, B E and F helices are shown and labeled. The heme b[L] of cyt b, 2Fe-2S cluster of the ISP, and the conserved residues that are in contact with bound inhibitors in the bc[1]-inhibitor complexes are also shown in the ball-and-stick form. Carbon atoms are colored yellow, oxygen red, nitrogen blue and sulfur green.
Figure 5.
Figure 5. Structural environments for the class Pf inhibitors. Bound inhibitors at the Q[o] pocket are shown in stick form and carbon atoms are shown in black, nitrogen in blue and oxygen in red. The inhibitors are enclosed in the cage of difference electron density calculated with refined phases with the inhibitor molecule omitted. Secondary structure elements around the Q[o] site of cyt b are given. Helices cd1, cd2, and ef as well as parts of C, B and E helices are shown and as labeled. The heme b[L] of cyt b and the iron-sulfur cluster of the ISP are also shown in the ball-and-stick form. Residues in the Q[o] pocket that are in direct contact with the inhibitor are rendered as stick models, in which carbon atoms are colored yellow, sulfur green, oxygen red and nitrogen blue. Those residues whose mutations render bc[1] inhibitor resistant and are in direct contact with the inhibitor are colored magenta for the carbon atoms. All difference maps are contoured at 3s except for that of UHDBT, which is at 2s. A, Stereo pair: stigmatellin binding environment. The stigmatellin is labeled as STG in red. B, Stereo pair: UHDBT binding environment. C, Stereo pair: famoxadone binding environment. The famoxadone is labeled FAM in red. D, Stereo pair: NQNO binding environment.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 341, 281-302) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20735493 T.Van Leeuwen, P.Van Nieuwenhuyse, B.Vanholme, W.Dermauw, R.Nauen, and L.Tirry (2011).
Parallel evolution of cytochrome b mediated bifenazate resistance in the citrus red mite Panonychus citri.
  Insect Mol Biol, 20, 135-140.  
19739941 G.Lenaz, and M.L.Genova (2010).
Structure and organization of mitochondrial respiratory complexes: a new understanding of an old subject.
  Antioxid Redox Signal, 12, 961.  
19928849 P.L.Zhao, L.Wang, X.L.Zhu, X.Huang, C.G.Zhan, J.W.Wu, and G.F.Yang (2010).
Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues.
  J Am Chem Soc, 132, 185-194.  
19189962 D.Baniulis, E.Yamashita, J.P.Whitelegge, A.I.Zatsman, M.P.Hendrich, S.S.Hasan, C.M.Ryan, and W.A.Cramer (2009).
Structure-Function, Stability, and Chemical Modification of the Cyanobacterial Cytochrome b6f Complex from Nostoc sp. PCC 7120.
  J Biol Chem, 284, 9861-9869.
PDB code: 2zt9
19810688 J.L.Cape, D.Aidasani, D.M.Kramer, and M.K.Bowman (2009).
Substrate redox potential controls superoxide production kinetics in the cytochrome bc complex.
  Biochemistry, 48, 10716-10723.  
19254042 J.W.Cooley, D.W.Lee, and F.Daldal (2009).
Across membrane communication between the Q(o) and Q(i) active sites of cytochrome bc(1).
  Biochemistry, 48, 1888-1899.  
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.  
19165831 P.Van Nieuwenhuyse, T.Van Leeuwen, J.Khajehali, B.Vanholme, and L.Tirry (2009).
Mutations in the mitochondrial cytochrome b of Tetranychus urticae Koch (Acari: Tetranychidae) confer cross-resistance between bifenazate and acequinocyl.
  Pest Manag Sci, 65, 404-412.  
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.  
18247319 D.Fernández-Ortuño, J.A.Torés, A.de Vicente, and A.Pérez-García (2008).
Field resistance to QoI fungicides in Podosphaera fusca is not supported by typical mutations in the mitochondrial cytochrome b gene.
  Pest Manag Sci, 64, 694-702.  
18953640 D.Xia, L.Esser, M.Elberry, F.Zhou, L.Yu, and C.A.Yu (2008).
The road to the crystal structure of the cytochrome bc (1) complex from the anoxigenic, photosynthetic bacterium Rhodobacter sphaeroides.
  J Bioenerg Biomembr, 40, 485-492.  
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
18264564 M.A.Colucci, C.J.Moody, and G.D.Couch (2008).
Natural and synthetic quinones and their reduction by the quinone reductase enzyme NQO1: from synthetic organic chemistry to compounds with anticancer potential.
  Org Biomol Chem, 6, 637-656.  
18093133 N.Fisher, and B.Meunier (2008).
Molecular basis of resistance to cytochrome bc1 inhibitors.
  FEMS Yeast Res, 8, 183-192.  
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.  
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.  
18408150 T.Van Leeuwen, B.Vanholme, S.Van Pottelberge, P.Van Nieuwenhuyse, R.Nauen, L.Tirry, and I.Denholm (2008).
Mitochondrial heteroplasmy and the evolution of insecticide resistance: non-Mendelian inheritance in action.
  Proc Natl Acad Sci U S A, 105, 5980-5985.  
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
17212344 H.Sierotzki, R.Frey, J.Wullschleger, S.Palermo, S.Karlin, J.Godwin, and U.Gisi (2007).
Cytochrome b gene sequence and structure of Pyrenophora teres and P. tritici-repentis and implications for QoI resistance.
  Pest Manag Sci, 63, 225-233.  
17971996 J.J.Newsome, M.A.Colucci, M.Hassani, H.D.Beall, and C.J.Moody (2007).
Benzimidazole- and benzothiazole-quinones: excellent substrates for NAD(P)H:quinone oxidoreductase 1.
  Org Biomol Chem, 5, 3665-3673.  
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.  
17530725 M.Schlitzer (2007).
Malaria Chemotherapeutics Part I: History of Antimalarial Drug Development, Currently Used Therapeutics, and Drugs in Clinical Development.
  ChemMedChem, 2, 944-986.  
17584742 R.Covian, K.Zwicker, F.A.Rotsaert, and B.L.Trumpower (2007).
Asymmetric and redox-specific binding of quinone and quinol at center N of the dimeric yeast cytochrome bc1 complex. Consequences for semiquinone stabilization.
  J Biol Chem, 282, 24198-24208.  
17561507 R.Covian, T.Kleinschroth, B.Ludwig, and B.L.Trumpower (2007).
Asymmetric binding of stigmatellin to the dimeric Paracoccus denitrificans bc1 complex: evidence for anti-cooperative ubiquinol oxidation and communication between center P ubiquinol oxidation sites.
  J Biol Chem, 282, 22289-22297.  
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.  
17143847 S.L.Toffolatti, L.Serrati, H.Sierotzki, U.Gisi, and A.Vercesi (2007).
Assessment of QoI resistance in Plasmopara viticola oospores.
  Pest Manag Sci, 63, 194-201.  
17253777 S.Rajagukguk, S.Yang, C.A.Yu, L.Yu, B.Durham, and F.Millett (2007).
Effect of mutations in the cytochrome b ef loop on the electron-transfer reactions of the Rieske iron-sulfur protein in the cytochrome bc1 complex.
  Biochemistry, 46, 1791-1798.  
17145759 T.Wenz, R.Covian, P.Hellwig, F.Macmillan, B.Meunier, B.L.Trumpower, and C.Hunte (2007).
Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III.
  J Biol Chem, 282, 3977-3988.  
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.  
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
16908520 R.Covian, and B.L.Trumpower (2006).
Regulatory interactions between ubiquinol oxidation and ubiquinone reduction sites in the dimeric cytochrome bc1 complex.
  J Biol Chem, 281, 30925-30932.  
16688790 V.Grasso, S.Palermo, H.Sierotzki, A.Garibaldi, and U.Gisi (2006).
Cytochrome b gene structure and consequences for resistance to Qo inhibitor fungicides in plant pathogens.
  Pest Manag Sci, 62, 465-472.  
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.  
15817393 A.Osyczka, C.C.Moser, and P.L.Dutton (2005).
Fixing the Q cycle.
  Trends Biochem Sci, 30, 176-182.  
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.  
15917236 M.W.Mather, E.Darrouzet, M.Valkova-Valchanova, J.W.Cooley, M.T.McIntosh, F.Daldal, and A.B.Vaidya (2005).
Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system.
  J Biol Chem, 280, 27458-27465.  
15912560 N.Fisher, and B.Meunier (2005).
Re-examination of inhibitor resistance conferred by Qo-site mutations in cytochrome b using yeast as a model system.
  Pest Manag Sci, 61, 973-978.  
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.