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PDBsum entry 3d31
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Transport protein
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PDB id
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3d31
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References listed in PDB file
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Key reference
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Title
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Structural basis of trans-Inhibition in a molybdate/tungstate abc transporter.
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Authors
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S.Gerber,
M.Comellas-Bigler,
B.A.Goetz,
K.P.Locher.
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Ref.
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Science, 2008,
321,
246-250.
[DOI no: ]
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PubMed id
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Abstract
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Transport across cellular membranes is an essential process that is catalyzed by
diverse membrane transport proteins. The turnover rates of certain transporters
are inhibited by their substrates in a process termed trans-inhibition, whose
structural basis is poorly understood. We present the crystal structure of a
molybdate/tungstate ABC transporter (ModBC) from Methanosarcina acetivorans in a
trans-inhibited state. The regulatory domains of the nucleotide-binding subunits
are in close contact and provide two oxyanion binding pockets at the shared
interface. By specifically binding to these pockets, molybdate or tungstate
prevent adenosine triphosphatase activity and lock the transporter in an
inward-facing conformation, with the catalytic motifs of the nucleotide-binding
domains separated. This allosteric effect prevents the transporter from
switching between the inward-facing and the outward-facing states, thus
interfering with the alternating access and release mechanism.
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Figure 1.
Fig. 1. ATPase activity and crystal structure of M. acetivorans
ModBC. (A) Relative ATP hydrolysis rates of MaModBC in the
presence of the oxyanions molybdate (open circles), tungstate
(solid diamonds), and sulfate (solid squares). Only molybdate
and tungstate are substrates of MaModBC. (B) Side view of
MaModBC in ribbon representation illustrating the arrangement of
the protein subunits. The gray box represents the approximate
position of the lipid membrane.
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Figure 4.
Fig. 4. TMD conformations as observed in the crystal structures
of MaModBC, AfModBC, and MalFGK. (A) Comparison of the TMDs
MaModB, AfModB, and MalFG. The key TM helices 4 and the coupling
helices of each transporter are colored yellow and blue,
respectively. The C  atoms of residues
MalG 183 and MalF 394 and the equivalent residues in MaModB
(165) and AfModB (153) are depicted as red spheres, with the
distances indicated. For clarity, only the cores of the TMDs are
shown for MalFG, and the NBDs have been removed. (B) Chemical
cross-linking of engineered cysteine residues at position 153 in
AfModB. Cross-linking was performed by CuCl[2] in detergent
solution, with or without ATP and o-vanadate (VO[4]). No Cu was
added to the control reaction. Protein markers are shown in the
left lane, with molecular masses indicated.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2008,
321,
246-250)
copyright 2008.
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