The Mycobacterium tuberculosis Very-Long-Chain Fatty Acyl-CoA Synthetase: Structural Basis for Housing Lipid Substrates Longer than the Enzyme
2012 (English)In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 20, no 6, 1062-1070 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2012. Vol. 20, no 6, 1062-1070 p.
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-79995DOI: 10.1016/j.str.2012.03.012ISI: 000305094500014OAI: oai:DiVA.org:su-79995DiVA: diva2:555313
FunderSwedish Research Council, 2010-5061Swedish Foundation for Strategic Research , FFL4