The Mycobacterium tuberculosis very-long-chain fatty acyl-CoA synthetase: structural basis for housing lipid substrates longer than the enzyme

Structure
Charlotta S AnderssonMartin Högbom

Abstract

The Mycobacterium tuberculosis acid-induced operon MymA encodes the fatty acyl-CoA synthetase FadD13 and is essential for virulence and intracellular growth of the pathogen. Fatty acyl-CoA synthetases activate lipids before entering into the metabolic pathways and are also involved in transmembrane lipid transport. Unlike soluble fatty acyl-CoA synthetases, but like the mammalian integral-membrane very-long-chain acyl-CoA synthetases, FadD13 accepts lipid substrates up to the maximum length tested (C(26)). Here, we show that FadD13 is a peripheral membrane protein. The structure and mutational studies reveal an arginine- and aromatic-rich surface patch as the site for membrane interaction. The protein accommodates a hydrophobic tunnel that extends from the active site toward the positive patch and is sealed by an arginine-rich lid-loop at the protein surface. Based on this and previous data, we propose a structural basis for accommodation of lipid substrates longer than the enzyme and transmembrane lipid transport by vectorial CoA-esterification.

References

Oct 1, 1996·Nature Structural Biology·W C Wimley, S H White
Nov 29, 1996·The Journal of Biological Chemistry·A UchiyamaT Hashimoto
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·D HirschH F Lodish
May 20, 1999·Nature Structural Biology·A PerrakisV S Lamzin
Jul 27, 2001·The Journal of Biological Chemistry·S E LewisJ E Schaffer
Jan 21, 2003·The Journal of Biological Chemistry·M Rachel RichardsJean E Schaffer
Sep 11, 2003·Microbiology and Molecular Biology Reviews : MMBR·Paul N Black, Concetta C DiRusso
Oct 1, 2003·The Biochemical Journal·Peter FraislJohannes Berger
Oct 22, 2003·FEMS Microbiology Letters·Amit SinghAnil K Tyagi
May 18, 2004·The Journal of Biological Chemistry·Yuko HisanagaMasashi Miyano
Aug 5, 2004·Journal of Lipid Research·Douglas G MashekTokuo T Yamamoto
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Nov 3, 2004·Biochimica Et Biophysica Acta·Hildur Palsdottir, Carola Hunte
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexei A VaginGarib N Murshudov
Jun 28, 2005·Nucleic Acids Research·Kevin BrysonDavid T Jones
Nov 1, 2005·Tuberculosis·Ramandeep SinghAnil K Tyagi
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Jun 10, 2006·Archives of Biochemistry and Biophysics·Peter FraislJohannes Berger
Aug 25, 2006·Biochimica Et Biophysica Acta·Anna Mulgrew-NesbittDiana Murray
May 15, 2007·Current Opinion in Lipidology·Ruth E Gimeno
Sep 1, 2007·Journal of Lipid Research·Paul A WatkinsJonathan Pevsner
Nov 1, 2007·Infectious Disorders Drug Targets·Clifton E BarryMichael R McNeil
Nov 21, 2007·The Journal of Biological Chemistry·Paul A Watkins
Feb 9, 2008·Biochimica Et Biophysica Acta·Concetta C DiRussoPaul N Black
Mar 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christian HoffmannHarald Engelhardt
Feb 3, 2009·Nature Chemical Biology·Pooja AroraRajesh S Gokhale
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jul 1, 2009·Nature Methods·Audur MagnusdottirHelena Berglund
Sep 5, 2009·Advances in Applied Microbiology·Devinder KaurMary Jackson
Oct 13, 2009·Biochimica Et Biophysica Acta·Lei O LiRosalind A Coleman
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 11, 2010·The Journal of Infectious Diseases·Kathleen Y DunphyLee W Riley
Dec 16, 2010·The Journal of Biological Chemistry·Changrong GeAmélie A Kelly

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Citations

Apr 30, 2013·The Journal of Biological Chemistry·Zhen LiuJames C Sacchettini
Aug 23, 2016·ACS Infectious Diseases·Misty L KuhnWayne F Anderson
Nov 9, 2016·Journal of Drug Targeting·Nzungize LambertJianping Xie
Sep 12, 2014·Molecular & Cellular Proteomics : MCP·Georgia Orfanoudaki, Anastassios Economou
Mar 9, 2018·Chembiochem : a European Journal of Chemical Biology·Franziska HemmerlingFrank Hahn
Nov 30, 2018·Bioscience Reports·Pierre SantucciStéphane Canaan
Aug 13, 2013·The Journal of Biological Chemistry·Olivia VergnolleJohn S Blanchard
Apr 5, 2013·The Journal of Biological Chemistry·Subhalaxmi NambiSandhya S Visweswariah
Jun 28, 2014·The Journal of Biological Chemistry·Nishad MatangeSandhya S Visweswariah
Jan 25, 2021·Archives of Biochemistry and Biophysics·Holly DykstraNing Wu

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