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PDBsum entry 2f43

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protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2f43
Jmol PyMol
Contents
Protein chains
480 a.a. *
471 a.a. *
124 a.a. *
Ligands
VO4
ATP
ADP
Metals
_MG ×2
* Residue conservation analysis
PDB id:
2f43
Name: Hydrolase
Title: Rat liver f1-atpase
Structure: Atp synthase alpha chain, mitochondrial. Chain: a. Atp synthase beta chain, mitochondrial. Chain: b. Atp synthase gamma chain, mitochondrial. Chain: g. Ec: 3.6.3.14
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver. Organ: liver
Biol. unit: Heptamer (from PDB file)
Resolution:
3.00Å     R-factor:   0.306     R-free:   0.320
Authors: C.Chen,A.K.Saxena,W.N.Simcoke,D.N.Garboczi,P.L.Pedersen, Y.H.Ko
Key ref:
C.Chen et al. (2006). Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. J Biol Chem, 281, 13777-13783. PubMed id: 16531409 DOI: 10.1074/jbc.M513369200
Date:
22-Nov-05     Release date:   07-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P15999  (ATPA_RAT) -  ATP synthase subunit alpha, mitochondrial
Seq:
Struc:
 
Seq:
Struc:
553 a.a.
480 a.a.
Protein chain
Pfam   ArchSchema ?
P10719  (ATPB_RAT) -  ATP synthase subunit beta, mitochondrial
Seq:
Struc:
 
Seq:
Struc:
529 a.a.
471 a.a.
Protein chain
Pfam   ArchSchema ?
P35435  (ATPG_RAT) -  ATP synthase subunit gamma, mitochondrial
Seq:
Struc:
273 a.a.
124 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: E.C.3.6.3.14  - H(+)-transporting two-sector ATPase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O + H+(In) = ADP + phosphate + H+(Out)
ATP
Bound ligand (Het Group name = ATP)
corresponds exactly
+ H(2)O
+ H(+)(In)
= ADP
+ phosphate
+ H(+)(Out)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   9 terms 
  Biological process     transport   9 terms 
  Biochemical function     nucleotide binding     9 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M513369200 J Biol Chem 281:13777-13783 (2006)
PubMed id: 16531409  
 
 
Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism.
C.Chen, A.K.Saxena, W.N.Simcoke, D.N.Garboczi, P.L.Pedersen, Y.H.Ko.
 
  ABSTRACT  
 
ATP synthesis from ADP, P(i), and Mg2+ takes place in mitochondria on the catalytic F1 unit (alpha3beta3gammedeltaepsilon) of the ATP synthase complex (F0F1), a remarkable nanomachine that interconverts electrochemical and mechanical energy, producing the high energy terminal bond of ATP. In currently available structural models of F1, the P-loop (amino acid residues 156GGAGVGKT163) contributes to substrate binding at the subunit catalytic sites. Here, we report the first transition state-like structure of F1 (ADP.V(i).Mg.F1) from rat liver that was crystallized with the phosphate (P(i)) analog vanadate (VO(3-)4 or V(i)). Compared with earlier "ground state" structures, this new F1 structure reveals that the active site region has undergone significant remodeling. P-loop residue alanine 158 is located much closer to V(i) than it is to P(i) in a previous structural model. No significant movements of P-loop residues of the subunit were observed at its analogous but noncatalytic sites. Under physiological conditions, such active site remodeling involving the small hydrophobic alanine residue may promote ATP synthesis by lowering the local dielectric constant, thus facilitating the dehydration of ADP and P(i). This new crystallographic study provides strong support for the catalytic mechanism of ATP synthesis deduced from earlier biochemical studies of liver F1 conducted in the presence of V(i) (Ko, Y. H., Bianchet, M., Amzel, L. M., and Pedersen, P. L. (1997) J. Biol. Chem. 272, 18875-18881; Ko, Y. H., Hong, S., and Pedersen, P. L. (1999) J. Biol. Chem. 274, 28853-28856).
 
  Selected figure(s)  
 
Figure 4.
FIGURE 4. A, plot of the difference in distance between -subunit atoms in the ADP·V[i]·Mg·F[1] transition state-like structure reported here aligned with the corresponding -subunit atoms of the ADP·P[i]·F[1] structure (10). The two -subunit structures were aligned and the average distance between corresponding amino acid atoms at each position throughout the sequences (residues 1-399 and 406-477) were calculated and plotted against residue number. The average distance that includes all difference calculations between all corresponding atoms in the two structures is only 0.36 Å. In contrast, difference calculations between corresponding atoms in the two structures that include the P-loop (^156GGAGVGKT^163) gave an average value of 1.0 Å (red line). B, overlay of a stick representation of the P-loop region of the subunit of the ADP·V[i]·Mg·F[1] transition state-like structure reported here with that of the subunit of the ADP·P[i]·F[1] structure (10). The conformational differences in the P-loops of the two structures are clearly delineated as are the relative positions of the -carbon atom of Ala^158. In addition, the overlay shows that V[i] (red) is much nearer the P-loop in the ADP·V[i]·Mg·F[1] structure than is P[i] (green)in the ADP·P[i]·F[1] structure.
Figure 7.
FIGURE 7. Proposed critical events in the formation of ATP catalyzed by the F[1] moiety of mitochondrial ATP synthase based on structural work reported here, our earlier collaborative structural studies (10), and our earlier biochemical studies (15, 16). In the top, ADP and P[i] are both able to bind to the catalytic F[1] moiety of rat liver ATP synthase in the absence of Mg^2+ (10). In the middle, when Mg^2+ enters it binds to the bound P[i], facilitating the formation of the transition state (16). ADP and MgP[i] are then brought closer together, whereas the methyl group of P-loop alanine 158 is brought into the active site. The lower dielectric environment facilitates the release of water as the ADP and MgP[i] are dehydrated to form ATPMg (bottom).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 13777-13783) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21396943 M.S.Manimekalai, A.Kumar, J.Jeyakanthan, and G.Grüber (2011).
The Transition-Like State and P(i) Entrance into the Catalytic A Subunit of the Biological Engine A-ATP Synthase.
  J Mol Biol, 408, 736-754.
PDB codes: 3nd8 3nd9 3p20
21383131 T.Beke-Somfai, P.Lincoln, and B.Nordén (2011).
Double-lock ratchet mechanism revealing the role of alphaSER-344 in FoF1 ATP synthase.
  Proc Natl Acad Sci U S A, 108, 4828-4833.  
19362069 L.Bae, and S.B.Vik (2009).
A more robust version of the Arginine 210-switched mutant in subunit a of the Escherichia coli ATP synthase.
  Biochim Biophys Acta, 1787, 1129-1134.  
19801635 V.Giorgio, E.Bisetto, M.E.Soriano, F.Dabbeni-Sala, E.Basso, V.Petronilli, M.A.Forte, P.Bernardi, and G.Lippe (2009).
Cyclophilin D modulates mitochondrial F0F1-ATP synthase by interacting with the lateral stalk of the complex.
  J Biol Chem, 284, 33982-33988.  
19240022 W.Li, L.E.Brudecki, A.E.Senior, and Z.Ahmad (2009).
Role of {alpha}-subunit VISIT-DG sequence residues Ser-347 and Gly-351 in the catalytic sites of Escherichia coli ATP synthase.
  J Biol Chem, 284, 10747-10754.  
18846414 A.F.Lodeyro, M.V.Castelli, and O.A.Roveri (2008).
ATP hydrolysis-driven H(+) translocation is stimulated by sulfate, a strong inhibitor of mitochondrial ATP synthesis.
  J Bioenerg Biomembr, 40, 269-279.  
19008861 D.Luo, T.Xu, R.P.Watson, D.Scherer-Becker, A.Sampath, W.Jahnke, S.S.Yeong, C.H.Wang, S.P.Lim, A.Strongin, S.G.Vasudevan, and J.Lescar (2008).
Insights into RNA unwinding and ATP hydrolysis by the flavivirus NS3 protein.
  EMBO J, 27, 3209-3219.
PDB codes: 2jlq 2jlr 2jls 2jlu 2jlv 2jlw 2jlx 2jly 2jlz
18958608 E.Bisetto, P.Picotti, V.Giorgio, V.Alverdi, I.Mavelli, and G.Lippe (2008).
Functional and stoichiometric analysis of subunit e in bovine heart mitochondrial F(0)F(1)ATP synthase.
  J Bioenerg Biomembr, 40, 257-267.  
18843528 M.Hüttemann, I.Lee, A.Pecinova, P.Pecina, K.Przyklenk, and J.W.Doan (2008).
Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease.
  J Bioenerg Biomembr, 40, 445-456.  
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.  
18175209 P.L.Pedersen (2007).
Transport ATPases into the year 2008: a brief overview related to types, structures, functions and roles in health and disease.
  J Bioenerg Biomembr, 39, 349-355.  
17879147 P.L.Pedersen (2007).
Warburg, me and Hexokinase 2: Multiple discoveries of key molecular events underlying one of cancers' most common phenotypes, the "Warburg Effect", i.e., elevated glycolysis in the presence of oxygen.
  J Bioenerg Biomembr, 39, 211-222.  
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 codes are shown on the right.

 

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