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PDBsum entry 5f15
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References listed in PDB file
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Key reference
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Title
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Structures of aminoarabinose transferase arnt suggest a molecular basis for lipid a glycosylation.
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Authors
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V.I.Petrou,
C.M.Herrera,
K.M.Schultz,
O.B.Clarke,
J.Vendome,
D.Tomasek,
S.Banerjee,
K.R.Rajashankar,
M.Belcher dufrisne,
B.Kloss,
E.Kloppmann,
B.Rost,
C.S.Klug,
M.S.Trent,
L.Shapiro,
F.Mancia.
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Ref.
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Science, 2016,
351,
608-612.
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PubMed id
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Abstract
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Polymyxins are antibiotics used in the last line of defense to combat
multidrug-resistant infections by Gram-negative bacteria. Polymyxin resistance
arises through charge modification of the bacterial outer membrane with the
attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose to lipid A, a
reaction catalyzed by the integral membrane lipid-to-lipid glycosyltransferase
4-amino-4-deoxy-L-arabinose transferase (ArnT). Here, we report crystal
structures of ArnT from Cupriavidus metallidurans, alone and in complex with the
lipid carrier undecaprenyl phosphate, at 2.8 and 3.2 angstrom resolution,
respectively. The structures show cavities for both lipidic substrates, which
converge at the active site. A structural rearrangement occurs on undecaprenyl
phosphate binding, which stabilizes the active site and likely allows lipid A
binding. Functional mutagenesis experiments based on these structures suggest a
mechanistic model for ArnT family enzymes.
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