Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation.

TitleStructures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation.
Publication TypeJournal Article
Year of Publication2016
AuthorsPetrou, VI, Herrera, CM, Schultz, KM, Clarke, OB, Vendome, J, Tomasek, D, Banerjee, S, Rajashankar, KR, Dufrisne, MBelcher, Kloss, B, Kloppmann, E, Rost, B, Klug, CS, M Trent, S, Shapiro, L, Mancia, F
JournalScience
Volume351
Issue6273
Pagination608-12
Date Published2016 Feb 5
ISSN1095-9203
Abstract

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.

DOI10.1126/science.aad1172
Alternate JournalScience
PubMed ID26912703
Grant ListAI064184 / AI / NIAID NIH HHS / United States
AI076322 / AI / NIAID NIH HHS / United States
P41 GM103403 / GM / NIGMS NIH HHS / United States
R01 GM111980 / GM / NIGMS NIH HHS / United States
S10 RR029205 / RR / NCRR NIH HHS / United States
U54 GM095315 / GM / NIGMS NIH HHS / United States