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PDBsum entry 1pp9

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1pp9
Jmol
Contents
Protein chains
443 a.a. *
424 a.a. *
365 a.a. *
241 a.a. *
196 a.a. *
99 a.a. *
75 a.a. *
66 a.a. *
42 a.a. *
62 a.a. *
Ligands
BHG ×6
AZI ×4
PEE ×9
PO4 ×2
GOL ×4
HEM ×4
SMA ×2
_UQ ×2
HEC ×2
FES ×2
CDL ×4
Waters ×1437
* Residue conservation analysis
PDB id:
1pp9
Name: Oxidoreductase
Title: Bovine cytochrome bc1 complex with stigmatellin bound
Structure: Ubiquinol-cytochromE C reductase complex core pro mitochondrial. Chain: a, n. Synonym: cytochrome bc1 complex, complex iii. Ubiquinol-cytochromE C reductase complex core pro mitochondrial. Chain: b, o. Synonym: complex iii subunit ii. Cytochrome b.
Source: Bos taurus. Cattle. Organism_taxid: 9913. Organism_taxid: 9913
Biol. unit: 20mer (from PQS)
Resolution:
2.10Å     R-factor:   0.250     R-free:   0.287
Authors: L.S.Huang,D.Cobessi,E.Y.Tung,E.A.Berry
Key ref:
L.S.Huang et al. (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. PubMed id: 16024040 DOI: 10.1016/j.jmb.2005.05.053
Date:
16-Jun-03     Release date:   20-Jul-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P31800  (QCR1_BOVIN) -  Cytochrome b-c1 complex subunit 1, mitochondrial
Seq:
Struc:
480 a.a.
443 a.a.
Protein chains
Pfam   ArchSchema ?
P23004  (QCR2_BOVIN) -  Cytochrome b-c1 complex subunit 2, mitochondrial
Seq:
Struc:
453 a.a.
424 a.a.*
Protein chains
Pfam   ArchSchema ?
P00157  (CYB_BOVIN) -  Cytochrome b
Seq:
Struc:
379 a.a.
365 a.a.
Protein chains
Pfam   ArchSchema ?
P00125  (CY1_BOVIN) -  Cytochrome c1, heme protein, mitochondrial
Seq:
Struc:
325 a.a.
241 a.a.
Protein chains
Pfam   ArchSchema ?
P13272  (UCRI_BOVIN) -  Cytochrome b-c1 complex subunit Rieske, mitochondrial
Seq:
Struc:
274 a.a.
196 a.a.
Protein chains
Pfam   ArchSchema ?
P00129  (QCR7_BOVIN) -  Cytochrome b-c1 complex subunit 7
Seq:
Struc:
111 a.a.
99 a.a.*
Protein chains
Pfam   ArchSchema ?
P13271  (QCR8_BOVIN) -  Cytochrome b-c1 complex subunit 8
Seq:
Struc:
82 a.a.
75 a.a.
Protein chains
Pfam   ArchSchema ?
P00126  (QCR6_BOVIN) -  Cytochrome b-c1 complex subunit 6, mitochondrial
Seq:
Struc:
91 a.a.
66 a.a.
Protein chains
Pfam   ArchSchema ?
P13272  (UCRI_BOVIN) -  Cytochrome b-c1 complex subunit Rieske, mitochondrial
Seq:
Struc:
274 a.a.
42 a.a.
Protein chains
Pfam   ArchSchema ?
P00130  (QCR9_BOVIN) -  Cytochrome b-c1 complex subunit 9
Seq:
Struc:
64 a.a.
62 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, R, V: 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 = SMA)
matches with 46.34% 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   7 terms 
  Biological process     oxidation-reduction process   18 terms 
  Biochemical function     catalytic activity     10 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2005.05.053 J Mol Biol 351:573-597 (2005)
PubMed id: 16024040  
 
 
Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern.
L.S.Huang, D.Cobessi, E.Y.Tung, E.A.Berry.
 
  ABSTRACT  
 
Antimycin A (antimycin), one of the first known and most potent inhibitors of the mitochondrial respiratory chain, binds to the quinone reduction site of the cytochrome bc1 complex. Structure-activity relationship studies have shown that the N-formylamino-salicyl-amide group is responsible for most of the binding specificity, and suggested that a low pKa for the phenolic OH group and an intramolecular H-bond between that OH and the carbonyl O of the salicylamide linkage are important. Two previous X-ray structures of antimycin bound to vertebrate bc1 complex gave conflicting results. A new structure reported here of the bovine mitochondrial bc1 complex at 2.28 A resolution with antimycin bound, allows us for the first time to reliably describe the binding of antimycin and shows that the intramolecular hydrogen bond described in solution and in the small-molecule structure is replaced by one involving the NH rather than carbonyl O of the amide linkage, with rotation of the amide group relative to the aromatic ring. The phenolic OH and formylamino N form H-bonds with conserved Asp228 of cytochrome b, and the formylamino O H-bonds via a water molecule to Lys227. A strong density, the right size and shape for a diatomic molecule is found between the other side of the dilactone ring and the alphaA helix.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. The structure of antimycin (stereo views). (a) From the small-molecule crystal structure42 (coordinates from the Cambridge Structure Database, CCDC # 125007). Hydrogen atoms have been removed from the carbon atoms for clarity. (b) From the structure 1PPJ, with the FSA ring and amide group in the plane of the picture. (C) As (b) but rotated 75° to view the dilactone ring nearly face-on. The electron density in (b) and (c) is a 2F[o] -F[c] map contoured at 2.1s (b) or 0.9s (c) from structure 1PPJ.
Figure 7.
Figure 7. Comparison of Q[i]-site residues and ligands in structures 1PPJ and Y21. The two structures were superimposed based on cytochrome b residues 32-51, 79-99, 113-145, 161-201, and 263-300. The backbone is shown for parts of transmembrane helices A (pink), D (red), and E (green), in color for 1PPJ and gray for Y21; as well as some of the linker region preceding helices A and D. Relevant side-chains are drawn with bonds and carbon atoms the same color as the backbone. Water molecules are shown as red spheres for 1PPJ and pink spheres for Y21. Antimycin from 1PPJ is shown as a purple ball-and stick figure with red oxygen atoms, while ubiquinone from structure Y21 is yellow. Note the relatively invariant positions of the backbone and side-chains, and the positioning of the ubiquinone ring over the amide moiety of antimycin.
 
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2005, 351, 573-597) copyright 2005.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20810427 A.D.Foote, P.A.Morin, J.W.Durban, R.L.Pitman, P.Wade, E.Willerslev, M.T.Gilbert, and R.R.da Fonseca (2011).
Positive selection on the killer whale mitogenome.
  Biol Lett, 7, 116-118.  
20938980 K.Illergård, A.Kauko, and A.Elofsson (2011).
Why are polar residues within the membrane core evolutionary conserved?
  Proteins, 79, 79-91.  
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
20544970 L.J.Smith, A.Kahraman, and J.M.Thornton (2010).
Heme proteins--diversity in structural characteristics, function, and folding.
  Proteins, 78, 2349-2368.  
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.  
19432984 E.Willerslev, M.Gilbert, J.Binladen, S.Ho, P.Campos, A.Ratan, L.Tomsho, R.da Fonseca, A.Sher, T.Kuznetsova, M.Nowak-Kemp, T.Roth, W.Miller, and S.Schuster (2009).
Analysis of complete mitochondrial genomes from extinct and extant rhinoceroses reveals lack of phylogenetic resolution.
  BMC Evol Biol, 9, 95.  
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.  
  19411865 M.A.Fath, A.R.Diers, N.Aykin-Burns, A.L.Simons, L.Hua, and D.R.Spitz (2009).
Mitochondrial electron transport chain blockers enhance 2-deoxy-D-glucose induced oxidative stress and cell killing in human colon carcinoma cells.
  Cancer Biol Ther, 8, 1228-1236.  
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.  
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.  
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.  
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.  
18093133 N.Fisher, and B.Meunier (2008).
Molecular basis of resistance to cytochrome bc1 inhibitors.
  FEMS Yeast Res, 8, 183-192.  
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.  
18318906 R.R.da Fonseca, W.E.Johnson, S.J.O'Brien, M.J.Ramos, and A.Antunes (2008).
The adaptive evolution of the mammalian mitochondrial genome.
  BMC Genomics, 9, 119.  
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.  
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.  
18021069 D.B.Zorov, N.K.Isaev, E.Y.Plotnikov, L.D.Zorova, E.V.Stelmashook, A.K.Vasileva, A.A.Arkhangelskaya, and T.G.Khrjapenkova (2007).
The mitochondrion as janus bifrons.
  Biochemistry (Mosc), 72, 1115-1126.  
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
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.  
17201689 T.Shikanai (2007).
Cyclic electron transport around photosystem I: genetic approaches.
  Annu Rev Plant Biol, 58, 199-217.  
17399709 V.P.Shinkarev, and C.A.Wraight (2007).
Intermonomer electron transfer in the bc1 complex dimer is controlled by the energized state and by impaired electron transfer between low and high potential hemes.
  FEBS Lett, 581, 1535-1541.  
17237049 Y.Park, and V.Helms (2007).
On the derivation of propensity scales for predicting exposed transmembrane residues of helical membrane proteins.
  Bioinformatics, 23, 701-708.  
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.  
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.  
16504567 T.M.Iverson (2006).
Evolution and unique bioenergetic mechanisms in oxygenic photosynthesis.
  Curr Opin Chem Biol, 10, 91.  
16641489 T.Páli, D.Bashtovyy, and D.Marsh (2006).
Stoichiometry of lipid interactions with transmembrane proteins--Deduced from the 3D structures.
  Protein Sci, 15, 1153-1161.  
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.  
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.