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The structural basis of fatty acid elongation by the ELOVL elongases

Authors
  • Nie, Laiyin1, 2
  • Pascoa, Tomas C.1
  • Pike, Ashley C. W.1
  • Bushell, Simon R.1, 3
  • Quigley, Andrew4, 5
  • Ruda, Gian Filippo1, 6
  • Chu, Amy1, 7
  • Cole, Victoria1, 8
  • Speedman, David1
  • Moreira, Tiago1
  • Shrestha, Leela1
  • Mukhopadhyay, Shubhashish M. M.1
  • Burgess-Brown, Nicola A.1
  • Love, James D.9, 10
  • Brennan, Paul E.1, 11
  • Carpenter, Elisabeth P.1, 12
  • 1 University of Oxford, Oxford, UK , Oxford (United Kingdom)
  • 2 CRELUX GmbH, Planegg-Martinsried, Germany , Planegg-Martinsried (Germany)
  • 3 Orbit Discovery, Oxford, UK , Oxford (United Kingdom)
  • 4 Membrane Protein Laboratory, Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot, UK , Didcot (United Kingdom)
  • 5 Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot, UK , Didcot (United Kingdom)
  • 6 Evotec Ltd, Milton, Abingdon, UK , Abingdon (United Kingdom)
  • 7 Oxford University, Oxford, UK , Oxford (United Kingdom)
  • 8 Genomics Centre, South African Medical Research Council, Cape Town, South Africa , Cape Town (South Africa)
  • 9 Albert Einstein College of Medicine, Department of Biochemistry, Bronx, NY, USA , Bronx (United States)
  • 10 Novo Nordisk A/S, Måløv, Denmark , Måløv (Denmark)
  • 11 Alzheimer’s Research UK Oxford Drug Discovery Institute, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK , Oxford (United Kingdom)
  • 12 Vertex Pharmaceuticals Ltd, Milton, Abingdon, UK , Abingdon (United Kingdom)
Type
Published Article
Journal
Nature Structural & Molecular Biology
Publisher
Springer Nature
Publication Date
Jun 10, 2021
Volume
28
Issue
6
Pages
512–520
Identifiers
DOI: 10.1038/s41594-021-00605-6
Source
Springer Nature
Disciplines
  • article
License
Yellow

Abstract

ELOVLs are membrane-embedded enzymes that elongate very long chain fatty acids, precursors of sphingolipids and ceramides. The first crystal structure of a human ELOVL reveals an unexpected reaction mechanism, suggesting potential approaches for inhibition in disease.

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