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PDBsum entry 2qlv
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Transferase/protein binding
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PDB id
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2qlv
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Contents |
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133 a.a.
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155 a.a.
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310 a.a.
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140 a.a.
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the heterotrimer core of saccharomyces cerevisiae ampk homologue snf1.
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Authors
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G.A.Amodeo,
M.J.Rudolph,
L.Tong.
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Ref.
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Nature, 2007,
449,
492-495.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2007,
449,
492-495)
copyright 2007.
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