3r44
From Proteopedia
Mycobacterium tuberculosis fatty acyl CoA synthetase
Structural highlights
Function[FAC13_MYCTU] Required for maintaining the appropriate mycolic acid composition and permeability of the envelope on its exposure to acidic pH. Catalyzes the activation of long-chain fatty acids as acyl-coenzyme A (acyl-CoA), which are then transferred to the multifunctional polyketide synthase (PKS) type III for further chain extension. It has preference for the fatty acid with long chain length in the following order: hexacosanoic acid (C26), tetracosanoic acid (C24) and palmitic acid (C16).[1] [2] [3] Publication Abstract from PubMedThe 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. The Mycobacterium tuberculosis Very-Long-Chain Fatty Acyl-CoA Synthetase: Structural Basis for Housing Lipid Substrates Longer than the Enzyme.,Andersson CS, Lundgren CA, Magnusdottir A, Ge C, Wieslander A, Molina DM, Hogbom M Structure. 2012 May 2. PMID:22560731[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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