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PDBsum entry 4p33
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References listed in PDB file
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Key reference
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Title
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Decoupling catalytic activity from biological function of the atpase that powers lipopolysaccharide transport.
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Authors
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D.J.Sherman,
M.B.Lazarus,
L.Murphy,
C.Liu,
S.Walker,
N.Ruiz,
D.Kahne.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
4982-4987.
[DOI no: ]
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PubMed id
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Abstract
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The cell surface of Gram-negative bacteria contains lipopolysaccharides (LPS),
which provide a barrier against the entry of many antibiotics. LPS assembly
involves a multiprotein LPS transport (Lpt) complex that spans from the
cytoplasm to the outer membrane. In this complex, an unusual ATP-binding
cassette transporter is thought to power the extraction of LPS from the outer
leaflet of the cytoplasmic membrane and its transport across the cell envelope.
We introduce changes into the nucleotide-binding domain, LptB, that inactivate
transporter function in vivo. We characterize these residues using biochemical
experiments combined with high-resolution crystal structures of LptB pre- and
post-ATP hydrolysis and suggest a role for an active site residue in phosphate
exit. We also identify a conserved residue that is not required for ATPase
activity but is essential for interaction with the transmembrane components. Our
studies establish the essentiality of ATP hydrolysis by LptB to power LPS
transport in cells and suggest strategies to inhibit transporter function away
from the LptB active site.
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