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PDBsum entry 1gaj
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Transport protein
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PDB id
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1gaj
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Contents |
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* Residue conservation analysis
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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 mj1267 ATP binding cassette reveal an induced-Fit effect at the atpase active site of an abc transporter.
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Authors
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N.Karpowich,
O.Martsinkevich,
L.Millen,
Y.R.Yuan,
P.L.Dai,
K.Macvey,
P.J.Thomas,
J.F.Hunt.
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Ref.
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Structure, 2001,
9,
571-586.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: ATP binding cassette (ABC) transporters are ubiquitously distributed
transmembrane solute pumps that play a causative role in numerous diseases.
Previous structures have defined the fold of the ABC and established the
flexibility of its alpha-helical subdomain. But the nature of the mechanical
changes that occur at each step of the chemical ATPase cycle have not been
defined. RESULTS: Crystal structures were determined of the MJ1267 ABC from
Methanococcus jannaschii in Mg-ADP-bound and nucleotide-free forms. Comparison
of these structures reveals an induced-fit effect at the active site likely to
be a consequence of nucleotide binding. In the Mg-ADP-bound structure, the loop
following the Walker B moves toward the Walker A (P-loop) coupled to backbone
conformational changes in the intervening "H-loop", which contains an
invariant histidine. These changes affect the region believed to mediate
intercassette interaction in the ABC transporter complex. Comparison of the
Mg-ADP-bound structure of MJ1267 to the ATP-bound structure of HisP suggests
that an outward rotation of the alpha-helical subdomain is coupled to the loss
of a molecular contact between the gamma-phosphate of ATP and an invariant
glutamine in a segment connecting this subdomain to the core of the cassette.
CONCLUSIONS: The induced-fit effect and rotation of the alpha-helical subdomain
may play a role in controlling the nucleotide-dependent change in
cassette-cassette interaction affinity believed to represent the power-stroke of
ABC transporters. Outward rotation of the alpha-helical subdomain also likely
facilitates Mg-ADP release after hydrolysis. The MJ1267 structures therefore
define features of the nucleotide-dependent conformational changes that drive
transmembrane transport in ABC transporters.
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Figure 4.
Figure 4. Cooperative Structural Interactions Involving
Phylogenetically Conserved Residues Stabilize Limiting
Conformations of the g-Phosphate LinkerH bonds in the
g-phosphate linker region identified based on having a
heteroatom separation =< 3.4 Å are represented by dotted orange
lines in the stereo pairs [57 and 58] showing:(a) The ATP-bound
structure of HisP [16].(b) The Mg-ADP-bound structure of MJ0796
[21].(c) The Mg-ADP-bound structure of MJ1267.(d) One of the two
NCS-related molecules in the pyrophosphate-bound structure of
MalK [17].Residues with side chains participating in alternative
H bonding networks with phylogenetically conserved Arg166 are
shown in cyan. Relative to MJ1267, homologous residues in the
g-phosphate linker region are offset by +1 in MJ0796, +11 in
HisP, and -1 in MalK, and homologous residues in the C terminus
of the ABCa subdomain are offset by -8 in MJ0796, +0 in HisP,
and -14 in MalK
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
571-586)
copyright 2001.
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