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PDBsum entry 1p84

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1p84
Jmol
Contents
Protein chains
431 a.a. *
352 a.a. *
385 a.a. *
246 a.a. *
185 a.a. *
74 a.a. *
125 a.a. *
93 a.a. *
55 a.a. *
127 a.a. *
107 a.a. *
Ligands
3PH ×2
UMQ
HEM ×3
DBT
UQ6
3PE ×2
PC1
CDL
FES
Waters ×326
* Residue conservation analysis
PDB id:
1p84
Name: Oxidoreductase
Title: Hdbt inhibited yeast cytochrome bc1 complex
Structure: Ubiquinol-cytochromE C reductase complex core protein i. Chain: a. Ubiquinol-cytochromE C reductase complex core protein 2. Chain: b. Cytochrome b. Chain: c. Cytochrome c1, heme protein.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Organelle: mitochondria. Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: 22mer (from PDB file)
Resolution:
2.50Å     R-factor:   0.228     R-free:   0.252
Authors: H.Palsdottir,C.G.Lojero,B.L.Trumpower,C.Hunte
Key ref:
H.Palsdottir et al. (2003). Structure of the yeast cytochrome bc1 complex with a hydroxyquinone anion Qo site inhibitor bound. J Biol Chem, 278, 31303-31311. PubMed id: 12782631 DOI: 10.1074/jbc.M302195200
Date:
06-May-03     Release date:   29-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07256  (QCR1_YEAST) -  Cytochrome b-c1 complex subunit 1, mitochondrial
Seq:
Struc:
457 a.a.
431 a.a.*
Protein chain
Pfam   ArchSchema ?
P07257  (QCR2_YEAST) -  Cytochrome b-c1 complex subunit 2, mitochondrial
Seq:
Struc:
368 a.a.
352 a.a.
Protein chain
Pfam   ArchSchema ?
P00163  (CYB_YEAST) -  Cytochrome b
Seq:
Struc:
385 a.a.
385 a.a.*
Protein chain
Pfam   ArchSchema ?
P07143  (CY1_YEAST) -  Cytochrome c1, heme protein, mitochondrial
Seq:
Struc:
309 a.a.
246 a.a.
Protein chain
Pfam   ArchSchema ?
P08067  (UCRI_YEAST) -  Cytochrome b-c1 complex subunit Rieske, mitochondrial
Seq:
Struc:
215 a.a.
185 a.a.
Protein chain
Pfam   ArchSchema ?
P00127  (QCR6_YEAST) -  Cytochrome b-c1 complex subunit 6
Seq:
Struc:
147 a.a.
74 a.a.
Protein chain
Pfam   ArchSchema ?
P00128  (QCR7_YEAST) -  Cytochrome b-c1 complex subunit 7
Seq:
Struc:
127 a.a.
125 a.a.
Protein chain
Pfam   ArchSchema ?
P08525  (QCR8_YEAST) -  Cytochrome b-c1 complex subunit 8
Seq:
Struc:
94 a.a.
93 a.a.
Protein chain
Pfam   ArchSchema ?
P22289  (QCR9_YEAST) -  Cytochrome b-c1 complex subunit 9
Seq:
Struc:
66 a.a.
55 a.a.
Protein chain
No UniProt id for this chain
Struc: 127 a.a.
Protein chain
No UniProt id for this chain
Struc: 107 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain E: 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 = UQ6)
matches with 53.00% similarity
+
2 × ferricytochrome c
Bound ligand (Het Group name = HEM)
matches with 63.00% 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   7 terms 
  Biochemical function     catalytic activity     12 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M302195200 J Biol Chem 278:31303-31311 (2003)
PubMed id: 12782631  
 
 
Structure of the yeast cytochrome bc1 complex with a hydroxyquinone anion Qo site inhibitor bound.
H.Palsdottir, C.G.Lojero, B.L.Trumpower, C.Hunte.
 
  ABSTRACT  
 
Bifurcated electron transfer during ubiquinol oxidation is the key reaction of cytochrome bc1 complex catalysis. Binding of the competitive inhibitor 5-n-heptyl-6-hydroxy-4,7-dioxobenzothiazole to the Qo site of the cytochrome bc1 complex from Saccharomyces cerevisiae was analyzed by x-ray crystallography. This alkylhydroxydioxobenzothiazole is bound in its ionized form as evident from the crystal structure and confirmed by spectroscopic analysis, consistent with a measured pKa = 6.1 of the hydroxy group in detergent micelles. Stabilizing forces for the hydroxyquinone anion inhibitor include a polarized hydrogen bond to the iron-sulfur cluster ligand His181 and on-edge interactions via weak hydrogen bonds with cytochrome b residue Tyr279. The hydroxy group of the latter contributes to stabilization of the Rieske protein in the b-position by donating a hydrogen bond. The reported pH dependence of inhibition with lower efficacy at alkaline pH is attributed to the protonation state of His181 with a pKa of 7.5. Glu272, a proposed primary ligand and proton acceptor of ubiquinol, is not bound to the carbonyl group of the hydroxydioxobenzothiazole ring but is rotated out of the binding pocket toward the heme bL propionate A, to which it is hydrogen-bonded via a single water molecule. The observed hydrogen bonding pattern provides experimental evidence for the previously proposed proton exit pathway involving the heme propionate and a chain of water molecules. Binding of the alkyl-6-hydroxy-4,7-dioxobenzothiazole is discussed as resembling an intermediate step of ubiquinol oxidation, supporting a single occupancy model at the Qo site.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The structure of the dimeric bc[1] complex depicted as a ribbon diagram. Ligands are shown as ball and stick models. HHDBT (yellow) is bound at the Q[o] site between the [2Fe-2S] cluster and the heme b[L]. Tightly bound phospholipid molecules (gray) are mainly present in the matrix-oriented leaflet of the phospholipid bilayer. The newly identified phosphatidylcholine molecule (PC, dark gray) at the intermembrane side marks the position of the enzyme with respect to the bilayer.
Figure 6.
FIG. 6. Apparent hydrogen bond network at the Q[o] site with the hydroxyquinone anion inhibitor bound. Glu272 is hydrogen-bonded to the heme b[L] propionate A, from which a proton exit pathway is formed by a chain of hydrogen-bonded water molecules, as depicted with the dotted lines. The arrow from Wat274 shows the proton exit pathway to bulk solvent. Hydrogen bonds stabilizing the ligand are shown as stippled lines. The position of Glu272 in the stigmatellin-inhibited bc[1] complex is indicated in yellow.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 31303-31311) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
20737064 F.Zsila, and I.Fitos (2010).
Combination of chiroptical, absorption and fluorescence spectroscopic methods reveals multiple, hydrophobicity-driven human serum albumin binding of the antimalarial atovaquone and related hydroxynaphthoquinone compounds.
  Org Biomol Chem, 8, 4905-4914.  
20544074 J.Gubbens, and A.I.de Kroon (2010).
Proteome-wide detection of phospholipid-protein interactions in mitochondria by photocrosslinking and click chemistry.
  Mol Biosyst, 6, 1751-1759.  
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.  
19660431 L.M.Hughes, R.Covian, G.W.Gribble, and B.L.Trumpower (2010).
Probing binding determinants in center P of the cytochrome bc(1) complex using novel hydroxy-naphthoquinones.
  Biochim Biophys Acta, 1797, 38-43.  
19413994 M.Schlame, and M.Ren (2009).
The role of cardiolipin in the structural organization of mitochondrial membranes.
  Biochim Biophys Acta, 1788, 2080-2083.  
19325183 R.Covian, and B.L.Trumpower (2009).
The rate-limiting step in the cytochrome bc1 complex (Ubiquinol-Cytochrome c Oxidoreductase) is not changed by inhibition of cytochrome b-dependent deprotonation: implications for the mechanism of ubiquinol oxidation at center P of the bc1 complex.
  J Biol Chem, 284, 14359-14367.  
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
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.  
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.  
  18034796 L.G.Kwa, D.Wegmann, B.Brügger, F.T.Wieland, G.Wanner, and P.Braun (2008).
Mutation of a single residue, beta-glutamate-20, alters protein-lipid interactions of light harvesting complex II.
  Mol Microbiol, 67, 63-77.  
18498758 M.G.Ding, C.A.Butler, S.A.Saracco, T.D.Fox, F.Godard, J.P.di Rago, and B.L.Trumpower (2008).
Introduction of cytochrome b mutations in Saccharomyces cerevisiae by a method that allows selection for both functional and non-functional cytochrome b proteins.
  Biochim Biophys Acta, 1777, 1147-1156.  
18093133 N.Fisher, and B.Meunier (2008).
Molecular basis of resistance to cytochrome bc1 inhibitors.
  FEMS Yeast Res, 8, 183-192.  
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
17383607 J.J.Kessl, N.V.Moskalev, G.W.Gribble, M.Nasr, S.R.Meshnick, and B.L.Trumpower (2007).
Parameters determining the relative efficacy of hydroxy-naphthoquinone inhibitors of the cytochrome bc1 complex.
  Biochim Biophys Acta, 1767, 319-326.  
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.  
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.  
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
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.  
16172928 A.J.Watson, A.V.Hughes, P.K.Fyfe, M.C.Wakeham, K.Holden-Dye, P.Heathcote, and M.R.Jones (2005).
On the role of basic residues in adapting the reaction centre-LH1 complex for growth at elevated temperatures in purple bacteria.
  Photosynth Res, 86, 81.  
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.  
14977419 A.R.Crofts (2004).
The cytochrome bc1 complex: function in the context of structure.
  Annu Rev Physiol, 66, 689-733.  
14612576 J.Regeimbal, S.Gleiter, B.L.Trumpower, C.A.Yu, M.Diwakar, D.P.Ballou, and J.C.Bardwell (2003).
Disulfide bond formation involves a quinhydrone-type charge-transfer complex.
  Proc Natl Acad Sci U S A, 100, 13779-13784.  
14622010 T.Merbitz-Zahradnik, K.Zwicker, J.H.Nett, T.A.Link, and B.L.Trumpower (2003).
Elimination of the disulfide bridge in the Rieske iron-sulfur protein allows assembly of the [2Fe-2S] cluster into the Rieske protein but damages the ubiquinol oxidation site in the cytochrome bc1 complex.
  Biochemistry, 42, 13637-13645.  
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.