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PDBsum entry 2oox
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protein ligands Protein-protein interface(s) links
Transferase PDB id
2oox

 

 

 

 

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Contents
Protein chains
128 a.a. *
93 a.a. *
324 a.a. *
Ligands
AMP ×2
Waters ×652
* Residue conservation analysis
PDB id:
2oox
Name: Transferase
Title: Crystal structure of the adenylate sensor from amp-activated protein kinase complexed with amp
Structure: Snf1-like protein kinase ssp2. Chain: a, c. Fragment: c-terminal domain: residues 440-576. Engineered: yes. Spcc1919.03c protein. Chain: b, d. Fragment: c-terminal domain: residues 203-298. Engineered: yes. Hypothetical protein c1556.08c in chromosome i.
Source: Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Strain: 972. Atcc: 38366. Gene: ssp2, spcc74.03c. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: spcc1919.03c.
Resolution:
2.60Å     R-factor:   0.210     R-free:   0.273
Authors: R.Townley,L.Shapiro
Key ref:
R.Townley and L.Shapiro (2007). Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase. Science, 315, 1726-1729. PubMed id: 17289942 DOI: 10.1126/science.1137503
Date:
26-Jan-07     Release date:   06-Feb-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O74536  (SNF1_SCHPO) -  SNF1-like protein kinase ssp2 from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Seq:
Struc: 		 
Seq:
Struc: 		576 a.a.
128 a.a.
Protein chains
Pfam   ArchSchema ?
P78789  (AAKB_SCHPO) -  5'-AMP-activated protein kinase subunit beta from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Seq:
Struc: 		298 a.a.
93 a.a.
Protein chains
Pfam   ArchSchema ?
Q10343  (AAKG_SCHPO) -  5'-AMP-activated protein kinase subunit gamma from Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Seq:
Struc: 		334 a.a.
324 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 A, C: E.C.2.7.11.1  - non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
Bound ligand (Het Group name = AMP)
matches with 85.19% similarity 		+ ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
Bound ligand (Het Group name = AMP)
matches with 85.19% similarity 		+ ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1126/science.1137503 Science 315:1726-1729 (2007)
PubMed id: 17289942  
 
 
Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase.
R.Townley, L.Shapiro.
 
  ABSTRACT  
 
The 5'-AMP (adenosine monophosphate)-activated protein kinase (AMPK) coordinates metabolic function with energy availability by responding to changes in intracellular ATP (adenosine triphosphate) and AMP concentrations. Here, we report crystal structures at 2.9 and 2.6 A resolution for ATP- and AMP-bound forms of a core alphabetagamma adenylate-binding domain from the fission yeast AMPK homolog. ATP and AMP bind competitively to a single site in the gamma subunit, with their respective phosphate groups positioned near function-impairing mutants. Unexpectedly, ATP binds without counterions, amplifying its electrostatic effects on a critical regulatory region where all three subunits converge.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Overall structure of the adenylate binding region from S. pombe AMPK with bound AMP. The ATP-bound form is nearly identical (fig. S6) and reveals no global structural changes attributable to nucleotide identity. (A) Ribbon diagram of a single heterotrimer, with , ß, and subunits colored yellow, blue, and green, respectively. The single molecule of bound AMP is shown in CPK representation, and connections to the GBD and KD at the N-termini of the ß and subunits, respectively, are indicated. (B) View rotated 90°, highlighting the adenylate binding entrance (AXP) and phosphate binding tunnel, which is capped on the putative KD-interaction surface by a polar flap from the ß subunit. The structure corresponds to a heterotrimer defined by limited proteolysis, as indicated in (C): hatched regions were excluded. Each of the two crystal forms reported here includes a dimer of trimers in the asymmetric unit (D). Analytical ultracentrifugation analysis also demonstrates a dimer of trimers configuration. 		Figure 3.
Fig. 3. [(A) and (B)] Functional mutations map within the phosphate binding tunnel, a large internal cavity that traverses the subunit, shown in red. The majority of known function-impairing mutants map to the surface of this tunnel, positioned between the terminal phosphate of the bound nucleotide and the putative kinase-binding face. Two orthogonal views are shown.
 
  The above figures are reprinted by permission from the AAAs: Science (2007, 315, 1726-1729) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22436748 D.G.Hardie, F.A.Ross, and S.A.Hawley (2012).
AMPK: a nutrient and energy sensor that maintains energy homeostasis.
  Nat Rev Mol Cell Biol, 13, 251-262.  
22659875 L.Chen, J.Wang, Y.Y.Zhang, S.F.Yan, D.Neumann, U.Schlattner, Z.X.Wang, and J.W.Wu (2012).
AMP-activated protein kinase undergoes nucleotide-dependent conformational changes.
  Nat Struct Mol Biol, 19, 716-718.
PDB codes: 4eag 4eai 4eaj 4eak 4eal
21067517 J.Jämsen, H.Tuominen, A.A.Baykov, and R.Lahti (2011).
Mutational analysis of residues in the regulatory CBS domains of Moorella thermoacetica pyrophosphatase corresponding to disease-related residues of human proteins.
  Biochem J, 433, 497-504.  
20959390 L.A.Martínez-Cruz, J.A.Encinar, P.Sevilla, I.Oyenarte, I.Gómez-García, D.Aguado-Llera, F.García-Blanco, J.Gómez, and J.L.Neira (2011).
Nucleotide-induced conformational transitions in the CBS domain protein MJ0729 of Methanocaldococcus jannaschii.
  Protein Eng Des Sel, 24, 161-169.  
21481774 L.Zhu, L.Chen, X.M.Zhou, Y.Y.Zhang, Y.J.Zhang, J.Zhao, S.R.Ji, J.W.Wu, and Y.Wu (2011).
Structural insights into the architecture and allostery of full-length AMP-activated protein kinase.
  Structure, 19, 515-522.  
21543851 N.Handa, T.Takagi, S.Saijo, S.Kishishita, D.Takaya, M.Toyama, T.Terada, M.Shirouzu, A.Suzuki, S.Lee, T.Yamauchi, M.Okada-Iwabu, M.Iwabu, T.Kadowaki, Y.Minokoshi, and S.Yokoyama (2011).
Structural basis for compound C inhibition of the human AMP-activated protein kinase α2 subunit kinase domain.
  Acta Crystallogr D Biol Crystallogr, 67, 480-487.
PDB codes: 2yza 3aqv
  20522000 B.Viollet, S.Horman, J.Leclerc, L.Lantier, M.Foretz, M.Billaud, S.Giri, and F.Andreelli (2010).
AMPK inhibition in health and disease.
  Crit Rev Biochem Mol Biol, 45, 276-295.  
21031502 C.Moffat, and M.Ellen Harper (2010).
Metabolic functions of AMPK: aspects of structure and of natural mutations in the regulatory gamma subunits.
  IUBMB Life, 62, 739-745.  
20154666 J.A.Zorn, and J.A.Wells (2010).
Turning enzymes ON with small molecules.
  Nat Chem Biol, 6, 179-188.  
20974912 J.S.Oakhill, Z.P.Chen, J.W.Scott, R.Steel, L.A.Castelli, N.Ling, S.L.Macaulay, and B.E.Kemp (2010).
β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK).
  Proc Natl Acad Sci U S A, 107, 19237-19241.  
20439164 J.Zhang, G.Vemuri, and J.Nielsen (2010).
Systems biology of energy homeostasis in yeast.
  Curr Opin Microbiol, 13, 382-388.  
20505668 J.Zheng, and Z.Jia (2010).
Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase.
  Nature, 465, 961-965.
PDB codes: 3eps 3lc6 3lcb
21145462 K.Moravcevic, J.M.Mendrola, K.R.Schmitz, Y.H.Wang, D.Slochower, P.A.Janmey, and M.A.Lemmon (2010).
Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids.
  Cell, 143, 966-977.
PDB codes: 3ose 3osm 3ost
19892703 N.Dzamko, B.J.van Denderen, A.L.Hevener, S.B.Jørgensen, J.Honeyman, S.Galic, Z.P.Chen, M.J.Watt, D.J.Campbell, G.R.Steinberg, and B.E.Kemp (2010).
AMPK beta1 deletion reduces appetite, preventing obesity and hepatic insulin resistance.
  J Biol Chem, 285, 115-122.  
20738312 Z.Wang, X.Wang, K.Qu, P.Zhu, N.Guo, R.Zhang, Z.Abliz, H.Yu, and H.Zhu (2010).
Binding of cordycepin monophosphate to AMP-activated protein kinase and its effect on AMP-activated protein kinase activation.
  Chem Biol Drug Des, 76, 340-344.  
19636075 A.De Angeli, O.Moran, S.Wege, S.Filleur, G.Ephritikhine, S.Thomine, H.Barbier-Brygoo, and F.Gambale (2009).
ATP binding to the C terminus of the Arabidopsis thaliana nitrate/proton antiporter, AtCLCa, regulates nitrate transport into plant vacuoles.
  J Biol Chem, 284, 26526-26532.  
19266076 A.E.Roux, A.Leroux, M.A.Alaamery, C.S.Hoffman, P.Chartrand, G.Ferbeyre, and L.A.Rokeach (2009).
Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast.
  PLoS Genet, 5, e1000408.  
19117544 A.McBride, S.Ghilagaber, A.Nikolaev, and D.G.Hardie (2009).
The glycogen-binding domain on the AMPK beta subunit allows the kinase to act as a glycogen sensor.
  Cell Metab, 9, 23-34.  
19416711 B.B.Zhang, G.Zhou, and C.Li (2009).
AMPK: an emerging drug target for diabetes and the metabolic syndrome.
  Cell Metab, 9, 407-416.  
19245650 J.S.Oakhill, J.W.Scott, and B.E.Kemp (2009).
Structure and function of AMP-activated protein kinase.
  Acta Physiol (Oxf), 196, 3.  
19474788 L.Chen, Z.H.Jiao, L.S.Zheng, Y.Y.Zhang, S.T.Xie, Z.X.Wang, and J.W.Wu (2009).
Structural insight into the autoinhibition mechanism of AMP-activated protein kinase.
  Nature, 459, 1146-1149.
PDB codes: 3dae 3h4j
19153081 M.Pimkin, J.Pimkina, and G.D.Markham (2009).
A regulatory role of the Bateman domain of IMP dehydrogenase in adenylate nucleotide biosynthesis.
  J Biol Chem, 284, 7960-7969.  
19651772 R.Scholz, M.Suter, T.Weimann, C.Polge, P.V.Konarev, R.F.Thali, R.D.Tuerk, B.Viollet, T.Wallimann, U.Schlattner, and D.Neumann (2009).
Homo-oligomerization and activation of AMP-activated protein kinase are mediated by the kinase domain alphaG-helix.
  J Biol Chem, 284, 27425-27437.  
  18765915 B.C.Jeong, K.S.Yoo, K.W.Jung, J.S.Shin, and H.K.Song (2008).
Purification, crystallization and preliminary X-ray diffraction analysis of a cystathionine beta-synthase domain-containing protein, CDCP2, from Arabidopsis thaliana.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 825-827.  
18480843 J.Qi, J.Gong, T.Zhao, J.Zhao, P.Lam, J.Ye, J.Z.Li, J.Wu, H.M.Zhou, and P.Li (2008).
Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue.
  EMBO J, 27, 1537-1548.  
19041767 J.S.Burg, D.W.Powell, R.Chai, A.L.Hughes, A.J.Link, and P.J.Espenshade (2008).
Insig regulates HMG-CoA reductase by controlling enzyme phosphorylation in fission yeast.
  Cell Metab, 8, 522-531.  
19022182 J.W.Scott, B.J.van Denderen, S.B.Jorgensen, J.E.Honeyman, G.R.Steinberg, J.S.Oakhill, T.J.Iseli, A.Koay, P.R.Gooley, D.Stapleton, and B.E.Kemp (2008).
Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes.
  Chem Biol, 15, 1220-1230.  
20161826 L.J.Reichling, S.M.Riddle, B.Mei, R.Bruinsma, T.A.Goossens, K.G.Huwiler, M.Maffitt, A.M.Newport, X.D.Qian, C.Ruttimann-Johnson, and K.W.Vogel (2008).
Homogenous fluorescent assays for characterizing small-molecule activators of AMP-activated protein kinase (AMPK).
  Curr Chem Genomics, 1, 34-42.  
  18931440 M.Lucas, D.Kortazar, E.Astigarraga, J.A.Fernández, J.M.Mato, M.L.Martínez-Chantar, and L.A.Martínez-Cruz (2008).
Purification, crystallization and preliminary X-ray diffraction analysis of the CBS-domain pair from the Methanococcus jannaschii protein MJ0100.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 936-941.  
18474591 M.Momcilovic, S.H.Iram, Y.Liu, and M.Carlson (2008).
Roles of the glycogen-binding domain and Snf4 in glucose inhibition of SNF1 protein kinase.
  J Biol Chem, 283, 19521-19529.  
18312263 M.Pimkin, and G.D.Markham (2008).
The CBS subdomain of inosine 5'-monophosphate dehydrogenase regulates purine nucleotide turnover.
  Mol Microbiol, 68, 342-359.  
18021800 M.Proudfoot, S.A.Sanders, A.Singer, R.Zhang, G.Brown, A.Binkowski, L.Xu, J.A.Lukin, A.G.Murzin, A.Joachimiak, C.H.Arrowsmith, A.M.Edwards, A.V.Savchenko, and A.F.Yakunin (2008).
Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain.
  J Mol Biol, 375, 301-315.
PDB codes: 1pvm 2qh1
18513746 N.P.King, T.M.Lee, M.R.Sawaya, D.Cascio, and T.O.Yeates (2008).
Structures and functional implications of an AMP-binding cystathionine beta-synthase domain protein from a hyperthermophilic archaeon.
  J Mol Biol, 380, 181-192.
PDB codes: 2rif 2rih
  18607087 P.Fernández-Millán, D.Kortazar, M.Lucas, M.L.Martínez-Chantar, E.Astigarraga, J.A.Fernández, O.Sabas, A.Albert, J.M.Mato, and L.A.Martínez-Cruz (2008).
Crystallization and preliminary crystallographic analysis of merohedrally twinned crystals of MJ0729, a CBS-domain protein from Methanococcus jannaschii.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 605-609.  
18303986 S.Zaman, S.I.Lippman, X.Zhao, and J.R.Broach (2008).
How Saccharomyces responds to nutrients.
  Annu Rev Genet, 42, 27-81.  
18314332 T.Williams, and J.E.Brenman (2008).
LKB1 and AMPK in cell polarity and division.
  Trends Cell Biol, 18, 193-198.  
17937905 B.E.Kemp, J.S.Oakhill, and J.W.Scott (2007).
AMPK structure and regulation from three angles.
  Structure, 15, 1161-1163.  
17851531 B.Xiao, R.Heath, P.Saiu, F.C.Leiper, P.Leone, C.Jing, P.A.Walker, L.Haire, J.F.Eccleston, C.T.Davis, S.R.Martin, D.Carling, and S.J.Gamblin (2007).
Structural basis for AMP binding to mammalian AMP-activated protein kinase.
  Nature, 449, 496-500.
PDB codes: 2v8q 2v92 2v9j
17983576 D.G.Hardie (2007).
AMPK and SNF1: Snuffing Out Stress.
  Cell Metab, 6, 339-340.  
17712357 D.G.Hardie (2007).
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.
  Nat Rev Mol Cell Biol, 8, 774-785.  
17851534 G.A.Amodeo, M.J.Rudolph, and L.Tong (2007).
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1.
  Nature, 449, 492-495.
PDB code: 2qlv
17518971 K.Lindgren, M.Ormestad, M.Persson, S.Martinsson, L.T.Svensson, and M.Mahlapuu (2007).
Regulation of the muscle-specific AMP-activated protein kinase alpha2beta2gamma3 complexes by AMP and implications of the mutations in the gamma3-subunit for the AMP dependence of the enzyme.
  FEBS J, 274, 2887-2896.  
17562318 S.Markovic, and R.Dutzler (2007).
The structure of the cytoplasmic domain of the chloride channel ClC-Ka reveals a conserved interaction interface.
  Structure, 15, 715-725.
PDB code: 2pfi
17937917 X.Jin, R.Townley, and L.Shapiro (2007).
Structural insight into AMPK regulation: ADP comes into play.
  Structure, 15, 1285-1295.
PDB codes: 2qr1 2qrc 2qrd 2qre
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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