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PDBsum entry 2qlv
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protein Protein-protein interface(s) links
Transferase/protein binding PDB id
2qlv

 

 

 

 

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Contents
Protein chains
133 a.a. *
155 a.a. *
310 a.a. *
140 a.a. *
Waters ×111
* Residue conservation analysis
PDB id:
2qlv
Name: Transferase/protein binding
Title: Crystal structure of the heterotrimer core of the s. Cerevisiae ampk homolog snf1
Structure: Carbon catabolite derepressing protein kinase. Chain: a, d. Engineered: yes. Protein sip2. Chain: b, e. Synonym: protein spm2. Engineered: yes. Nuclear protein snf4. Chain: c, f.
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: snf1, cat1, ccr1, glc2, pas14. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: sip2, spm2. Gene: snf4, cat3.
Resolution:
2.60Å     R-factor:   0.239     R-free:   0.299
Authors: G.A.Amodeo,M.J.Rudolph,L.Tong
Key ref:
G.A.Amodeo et al. (2007). Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1. Nature, 449, 492-495. PubMed id: 17851534 DOI: 10.1038/nature06127
Date:
13-Jul-07     Release date:   25-Sep-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06782  (SNF1_YEAST) -  Carbon catabolite-derepressing protein kinase from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		 
Seq:
Struc: 		633 a.a.
133 a.a.
Protein chain
Pfam   ArchSchema ?
P34164  (SIP2_YEAST) -  SNF1 protein kinase subunit beta-2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		415 a.a.
155 a.a.
Protein chains
Pfam   ArchSchema ?
P12904  (AAKG_YEAST) -  5'-AMP-activated protein kinase subunit gamma from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		322 a.a.
310 a.a.
Protein chain
Pfam   ArchSchema ?
P34164  (SIP2_YEAST) -  SNF1 protein kinase subunit beta-2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Seq:
Struc: 		415 a.a.
140 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, D: 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]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
   Enzyme class 2: Chains B, C, E, F: E.C.?
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/nature06127 Nature 449:492-495 (2007)
PubMed id: 17851534  
 
 
Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1.
G.A.Amodeo, M.J.Rudolph, L.Tong.
 
  ABSTRACT  
 
AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 A resolution of the heterotrimer core of SNF1. The ligand-binding site in the gamma-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the beta-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the alpha-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the alpha- and gamma-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state.
 
  Selected figure(s)  
 
Figure 2.
Figure 2: Large conformational differences for the Bateman2 domain of Snf4. a, Structure of the Snf4 subunit, consisting of a Bateman1:Bateman2 'heterodimer'. The secondary structure elements are named in accordance with the system devised earlier^26. b, Structure of the Bateman2-domain dimer of Snf4 (ref. 26). The two monomers are arranged in a head-to-tail fashion. c, Overlay of the structures of the Bateman2 domain in full-length Snf4 (in green) and in the homodimer (in grey). Produced with Ribbons^30. 		Figure 3.
Figure 3: Structure of the ligand-binding site in S. cerevisiae Snf4. Stereo-view overlay of the structures of the -subunits of S. cerevisiae SNF1 (Snf4, in green) and S. pombe AMPK (in grey)^9. The position of AMP is observed in the S. pombe structure^9, as well as from our studies. Residues that could interact with AMP are shown, and those that are equivalent to disease-causing mutations in mammalian -subunits are labelled in red. Produced with Ribbons^30.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2007, 449, 492-495) copyright 2007.  
  Figures were selected by an automated process.  

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
21464305 A.Ruiz, X.Xu, and M.Carlson (2011).
Roles of two protein phosphatases, Reg1-Glc7 and Sit4, and glycogen synthesis in regulation of SNF1 protein kinase.
  Proc Natl Acad Sci U S A, 108, 6349-6354.  
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
20154666 J.A.Zorn, and J.A.Wells (2010).
Turning enzymes ON with small molecules.
  Nat Chem Biol, 6, 179-188.  
20439164 J.Zhang, G.Vemuri, and J.Nielsen (2010).
Systems biology of energy homeostasis in yeast.
  Curr Opin Microbiol, 13, 382-388.  
20545859 J.Zhang, L.Olsson, and J.Nielsen (2010).
The beta-subunits of the Snf1 kinase in Saccharomyces cerevisiae, Gal83 and Sip2, but not Sip1, are redundant in glucose derepression and regulation of sterol biosynthesis.
  Mol Microbiol, 77, 371-383.  
20685962 N.Kazgan, T.Williams, L.J.Forsberg, and J.E.Brenman (2010).
Identification of a nuclear export signal in the catalytic subunit of AMP-activated protein kinase.
  Mol Biol Cell, 21, 3433-3442.  
  19557293 A.Gruzman, G.Babai, and S.Sasson (2009).
Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations.
  Rev Diabet Stud, 6, 13-36.  
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
19581628 M.Bendayan, I.Londono, B.E.Kemp, G.D.Hardie, N.Ruderman, and M.Prentki (2009).
Association of AMP-activated protein kinase subunits with glycogen particles as revealed in situ by immunoelectron microscopy.
  J Histochem Cytochem, 57, 963-971.  
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.  
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.  
  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.  
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.  
18079111 T.J.Iseli, J.S.Oakhill, M.F.Bailey, S.Wee, M.Walter, B.J.van Denderen, L.A.Castelli, F.Katsis, L.A.Witters, D.Stapleton, S.L.Macaulay, B.J.Michell, and B.E.Kemp (2008).
AMP-activated protein kinase subunit interactions: beta1:gamma1 association requires beta1 Thr-263 and Tyr-267.
  J Biol Chem, 283, 4799-4807.  
18314332 T.Williams, and J.E.Brenman (2008).
LKB1 and AMPK in cell polarity and division.
  Trends Cell Biol, 18, 193-198.  
18757815 T.Ye, K.Elbing, and S.Hohmann (2008).
The pathway by which the yeast protein kinase Snf1p controls acquisition of sodium tolerance is different from that mediating glucose regulation.
  Microbiology, 154, 2814-2826.  
18372250 U.Riek, R.Scholz, P.Konarev, A.Rufer, M.Suter, A.Nazabal, P.Ringler, M.Chami, S.A.Müller, D.Neumann, M.Forstner, M.Hennig, R.Zenobi, A.Engel, D.Svergun, U.Schlattner, and T.Wallimann (2008).
Structural properties of AMP-activated protein kinase: dimerization, molecular shape, and changes upon ligand binding.
  J Biol Chem, 283, 18331-18343.  
17937905 B.E.Kemp, J.S.Oakhill, and J.W.Scott (2007).
AMPK structure and regulation from three angles.
  Structure, 15, 1161-1163.  
17983576 D.G.Hardie (2007).
AMPK and SNF1: Snuffing Out Stress.
  Cell Metab, 6, 339-340.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
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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