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PDBsum entry 2oox
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Contents |
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128 a.a.
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93 a.a.
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324 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 structures of the adenylate sensor from fission yeast AMP-Activated protein kinase.
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Authors
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R.Townley,
L.Shapiro.
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Ref.
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Science, 2007,
315,
1726-1729.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2007,
315,
1726-1729)
copyright 2007.
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