Structures of aminoarabinose transferase ArnT suggest a molecular basis for lipid A glycosylation-Reference-Cited by-同舟云学术

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

Published:2016-02-05 Issue:6273 Volume:351 Page:608-612
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Petrou Vasileios I.¹,Herrera Carmen M.²,Schultz Kathryn M.³,Clarke Oliver B.⁴,Vendome Jérémie⁴⁵,Tomasek David¹,Banerjee Surajit⁶,Rajashankar Kanagalaghatta R.⁶,Belcher Dufrisne Meagan¹,Kloss Brian⁷,Kloppmann Edda⁸,Rost Burkhard⁸⁹,Klug Candice S.³,Trent M. Stephen²,Shapiro Lawrence⁴,Mancia Filippo¹

Affiliation:

1. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.

2. Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, GA 30602, USA.

3. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

4. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.

5. Department of Systems Biology, Columbia University, New York, NY 10032, USA.

6. Department of Chemistry and Chemical Biology, Cornell University, Northeastern Collaborative Access Team, Advanced Photon Source, Argonne, IL 60439, USA.

7. New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, NY 10027, USA.

8. Department of Informatics, Bioinformatics and Computational Biology, Technische Universität München, Boltzmannstrasse 3, 85748 Garching, Germany.

9. Institute for Advanced Study (TUM-IAS), Technische Universität München, Boltzmannstrasse 3, 85748 Garching, Germany.

Abstract

A bacterial defense mechanism Polymyxins are antibiotics that disrupt the bacterial cell membrane and are used to treat multidrug-resistant infections. A bacterial enzyme called ArnT can mediate resistance to polymyxins by transferring a sugar group from a lipid carrier to lipid A, a component of the bacterial outer membrane. Petrou et al. described structures of ArnT alone and in complex with a lipid carrier and identified a cavity where lipid A probably binds. Insights into the enzyme mechanism could be exploited to design drugs that combat polymyxin resistance. Science , this issue p. 608

Funder

National Institute of General Medical Sciences (NIGMS)

NYCOMPS

NIGMS

NIH

Army Research Office

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference46 articles.

1. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review