PDBsum entry 2jj1

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
Jmol PyMol
Protein chains
(+ 0 more) 487 a.a. *
(+ 0 more) 467 a.a. *
167 a.a. *
ANP ×8
GOL ×12
ADP ×2
AZI ×2
PO4 ×2
PIT ×2
_MG ×10
Waters ×1139
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: The structure of f1-atpase inhibited by piceatannol.
Structure: Atp synthase subunit alpha heart isoform. Chain: a, b, c, h, i, j. Fragment: residues 44-553. Synonym: atp synthase alpha chain heart isoform. Atp synthase subunit beta. Chain: d, e, f, k, l, m. Fragment: residues 47-528. Synonym: atp synthase beta chain. Atp synthase gamma chain.
Source: Bos taurus. Bovine. Organism_taxid: 9913. Organ: heart. Organ: heart
2.70Å     R-factor:   0.205     R-free:   0.269
Authors: J.R.Gledhill,M.G.Montgomery,A.G.W.Leslie,J.E.Walker
Key ref:
J.R.Gledhill et al. (2007). Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols. Proc Natl Acad Sci U S A, 104, 13632-13637. PubMed id: 17698806 DOI: 10.1073/pnas.0706290104
03-Jul-07     Release date:   21-Aug-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19483  (ATPA_BOVIN) -  ATP synthase subunit alpha, mitochondrial
553 a.a.
487 a.a.
Protein chains
Pfam   ArchSchema ?
P00829  (ATPB_BOVIN) -  ATP synthase subunit beta, mitochondrial
528 a.a.
467 a.a.
Protein chains
Pfam   ArchSchema ?
P05631  (ATPG_BOVIN) -  ATP synthase subunit gamma, mitochondrial
298 a.a.
167 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains D, E, F, K, L, M: E.C.  - H(+)-transporting two-sector ATPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O + H+(In) = ADP + phosphate + H+(Out)
+ H(2)O
+ H(+)(In)
Bound ligand (Het Group name = ADP)
corresponds exactly
Bound ligand (Het Group name = PO4)
corresponds exactly
+ H(+)(Out)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   14 terms 
  Biological process     transport   13 terms 
  Biochemical function     nucleotide binding     11 terms  


DOI no: 10.1073/pnas.0706290104 Proc Natl Acad Sci U S A 104:13632-13637 (2007)
PubMed id: 17698806  
Mechanism of inhibition of bovine F1-ATPase by resveratrol and related polyphenols.
J.R.Gledhill, M.G.Montgomery, A.G.Leslie, J.E.Walker.
The structures of F(1)-ATPase from bovine heart mitochondria inhibited with the dietary phytopolyphenol, resveratrol, and with the related polyphenols quercetin and piceatannol have been determined at 2.3-, 2.4- and 2.7-A resolution, respectively. The inhibitors bind to a common site in the inside surface of an annulus made from loops in the three alpha- and three beta-subunits beneath the "crown" of beta-strands in their N-terminal domains. This region of F(1)-ATPase forms a bearing to allow the rotation of the tip of the gamma-subunit inside the annulus during catalysis. The binding site is a hydrophobic pocket between the C-terminal tip of the gamma-subunit and the beta(TP) subunit, and the inhibitors are bound via H-bonds mostly to their hydroxyl moieties mediated by bound water molecules and by hydrophobic interactions. There are no equivalent sites between the gamma-subunit and either the beta(DP) or the beta(E) subunit. The inhibitors probably prevent both the synthetic and hydrolytic activities of the enzyme by blocking both senses of rotation of the gamma-subunit. The beneficial effects of dietary resveratrol may derive in part by preventing mitochondrial ATP synthesis in tumor cells, thereby inducing apoptosis.
  Selected figure(s)  
Figure 1.
Fig. 1. Structures of polyphenol inhibitors of bovine F[1]-ATPase. (I) Resveratrol. (II) Piceatannol. (III) Quercetin.
Figure 3.
Fig. 3. Comparison of the modes of binding to bovine F[1]-ATPase of piceatannol and quercetin with that of resveratrol. (A) Major binding modes of resveratrol (green) and piceatannol (gray). (B) Major binding mode of resveratrol (green) and cis-quercetin (gray).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21285292 C.Beauloye, L.Bertrand, S.Horman, and L.Hue (2011).
AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure.
  Cardiovasc Res, 90, 224-233.  
21265739 D.G.Hardie (2011).
AMP-activated protein kinase: a cellular energy sensor with a key role in metabolic disorders and in cancer.
  Biochem Soc Trans, 39, 1.  
21481781 K.Okazaki, and S.Takada (2011).
Structural Comparison of F(1)-ATPase: Interplay among Enzyme Structures, Catalysis, and Rotations.
  Structure, 19, 588-598.  
19768783 A.C.Stelzer, R.W.Frazee, C.Van Huis, J.Cleary, A.W.Opipari, G.D.Glick, and H.M.Al-Hashimi (2010).
NMR studies of an immunomodulatory benzodiazepine binding to its molecular target on the mitochondrial F(1)F(0)-ATPase.
  Biopolymers, 93, 85-92.  
21102633 D.Herranz, and M.Serrano (2010).
SIRT1: recent lessons from mouse models.
  Nat Rev Cancer, 10, 819-823.  
20087853 H.M.Eid, L.C.Martineau, A.Saleem, A.Muhammad, D.Vallerand, A.Benhaddou-Andaloussi, L.Nistor, A.Afshar, J.T.Arnason, and P.S.Haddad (2010).
Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea.
  Mol Nutr Food Res, 54, 991.  
  20848587 L.Mouchiroud, L.Molin, N.Dallière, and F.Solari (2010).
Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging.
  Biofactors, 36, 377-382.  
20412062 L.Notari, N.Arakaki, D.Mueller, S.Meier, J.Amaral, and S.P.Becerra (2010).
Pigment epithelium-derived factor binds to cell-surface F(1)-ATP synthase.
  FEBS J, 277, 2192-2205.  
20190133 M.D.Fullerton, and G.R.Steinberg (2010).
SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol.
  Diabetes, 59, 551-553.  
20519126 S.A.Hawley, F.A.Ross, C.Chevtzoff, K.A.Green, A.Evans, S.Fogarty, M.C.Towler, L.J.Brown, O.A.Ogunbayo, A.M.Evans, and D.G.Hardie (2010).
Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation.
  Cell Metab, 11, 554-565.  
20467424 S.Fulda, L.Galluzzi, and G.Kroemer (2010).
Targeting mitochondria for cancer therapy.
  Nat Rev Drug Discov, 9, 447-464.  
20206201 S.J.Ralph, S.Rodríguez-Enríquez, J.Neuzil, E.Saavedra, and R.Moreno-Sánchez (2010).
The causes of cancer revisited: "mitochondrial malignancy" and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy.
  Mol Aspects Med, 31, 145-170.  
20100509 T.F.Laughlin, and Z.Ahmad (2010).
Inhibition of Escherichia coli ATP synthase by amphibian antimicrobial peptides.
  Int J Biol Macromol, 46, 367-374.  
19441016 J.Bernatoniene, S.Trumbeckaite, D.Majiene, R.Baniene, G.Baliutyte, A.Savickas, and A.Toleikis (2009).
The effect of crataegus fruit extract and some of its flavonoids on mitochondrial oxidative phosphorylation in the heart.
  Phytother Res, 23, 1701-1707.  
19477165 L.S.Chen, B.J.Nowak, M.L.Ayres, N.L.Krett, S.T.Rosen, S.Zhang, and V.Gandhi (2009).
Inhibition of ATP synthase by chlorinated adenosine analogue.
  Biochem Pharmacol, 78, 583-591.  
19423706 M.Vollmar, D.Schlieper, M.Winn, C.Büchner, and G.Groth (2009).
Structure of the c14 rotor ring of the proton translocating chloroplast ATP synthase.
  J Biol Chem, 284, 18228-18235.
PDB code: 2w5j
19432534 S.Pervaiz, and A.L.Holme (2009).
Resveratrol: its biologic targets and functional activity.
  Antioxid Redox Signal, 11, 2851-2897.  
18837061 A.Mattarei, L.Biasutto, E.Marotta, U.De Marchi, N.Sassi, S.Garbisa, M.Zoratti, and C.Paradisi (2008).
A mitochondriotropic derivative of quercetin: a strategy to increase the effectiveness of polyphenols.
  Chembiochem, 9, 2633-2642.  
18455976 K.T.Howitz, and D.A.Sinclair (2008).
Xenohormesis: sensing the chemical cues of other species.
  Cell, 133, 387-391.  
  19276535 L.Potenza, C.Calcabrini, R.De Bellis, U.Mancini, L.Cucchiarini, and M.Dachà (2008).
Effect of quercetin on oxidative nuclear and mitochondrial DNA damage.
  Biofactors, 33, 33-48.  
18602018 P.L.Toogood (2008).
Mitochondrial drugs.
  Curr Opin Chem Biol, 12, 457-463.  
19052322 S.Hong, and P.L.Pedersen (2008).
ATP synthase and the actions of inhibitors utilized to study its roles in human health, disease, and other scientific areas.
  Microbiol Mol Biol Rev, 72, 590.  
17895376 J.R.Gledhill, M.G.Montgomery, A.G.Leslie, and J.E.Walker (2007).
How the regulatory protein, IF(1), inhibits F(1)-ATPase from bovine mitochondria.
  Proc Natl Acad Sci U S A, 104, 15671-15676.
PDB code: 2v7q
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.