From Proteopedia
proteopedia linkproteopedia link Introduction
in Mycobacterium Tuberculosis is an ACSVL (Acyl-CoA synthetases very long) peripheral membrane protein. ACS proteins activate lipids and fatty acids before going into metabolic pathways. FadD13 is soluble unlike other ACSVL proteins. FadD13 contains a hydrophobic tunnel for fatty acids to bind to, as well as an arginine rich lid loop that binds to the cell membrane. The binding of ATP causes structural changes promoting the binding of the hydrophobic substrates. Formation of an acyl-adenylate intermediate induces a 140 degree rotation of the small domain and binding of CoA for production of the final product, a fatty acyl-CoA thioester.
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Background
Mycobacterium Tuberculosis is the causative agent of Tuberculosis commonly abbreviated TB. TB causes approximately 1.4 million deaths every year. The cost for treatment of patients with TB between the years 2010-2015 was approximately 16 billion dollars. TB is spread through the air, not by contact. There are two forms of TB, latent TB and TB disease.
Structural highlights
There are many portions of the FadD13 enzyme the play very pivotal roles in its function. The first important structural point of note is that there are two sub units, the larger N-terminal sub unit () and the smaller C-terminal sub unit () held together by a six amino acid linker ().The allows for either ATP or AMP to bind and activate FadD13. The next major region of note is the hydrophobic tunnel which allows for lipid binding up to 26 carbons in length. The hydrophobic tunnel is capped by and arginine and aromatic-rich surface patch.
Function
The FadD13 enzyme functions to activate lipids before going into metabolic pathways. This is done by ATP/AMP binding to the . Once ATP/AMP is bound the long lipid chain up to 26 carbons may bind in the hydrophobic portion of the enzyme. Upon binding of the substrate, the C terminal swings up to close off the tunnel. From There CoA can bind to produce the final product, an acyl-CoA Thioester. The lipid can now move transversely throughout the membrane and throughout the rest of the cell.
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References
Andersson, C.S., Lundgren, C.A.K., Magnusdottir, A., Ge, C., Weislander, A., Molina, D., Hogbom, M. (2012)The Mycobacterium tuberculosis Very-Long-Chain Fatty Acyl-CoA Synthetase: structural Basis for Housing Lipid Substrates longer than the Enzyme. Cell Press,1062-1070
