3e53
From Proteopedia
Crystal structure of N-terminal domain of a Fatty Acyl AMP Ligase FAAL28 from Mycobacterium tuberculosis
Structural highlights
Function[FAA28_MYCTO] Catalyzes the activation of long-chain fatty acids (C22-24 fatty acids) as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension. Involved in the biosynthesis of mycoserates (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe recent discovery of fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis (Mtb) provided a new perspective of fatty acid activation. These proteins convert fatty acids to the corresponding adenylates, which are intermediates of acyl-CoA-synthesizing fatty acyl-CoA ligases (FACLs). Presently, it is not evident how obligate pathogens such as Mtb have evolved such new themes of functional versatility and whether the activation of fatty acids to acyladenylates could indeed be a general mechanism. Here, based on elucidation of the first structure of an FAAL protein and by generating loss-of-function and gain-of-function mutants that interconvert FAAL and FACL activities, we demonstrate that an insertion motif dictates formation of acyladenylate. Because FAALs in Mtb are crucial nodes in the biosynthetic network of virulent lipids, inhibitors directed against these proteins provide a unique multipronged approach to simultaneously disrupting several pathways. Mechanistic and functional insights into fatty acid activation in Mycobacterium tuberculosis.,Arora P, Goyal A, Natarajan VT, Rajakumara E, Verma P, Gupta R, Yousuf M, Trivedi OA, Mohanty D, Tyagi A, Sankaranarayanan R, Gokhale RS Nat Chem Biol. 2009 Mar;5(3):166-73. Epub 2009 Feb 1. PMID:19182784[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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