3t5a | pdb_00003t5a
Crystal structure of N-terminal domain of FAAL28 G330W mutant from Mycobacterium tuberculosis
Structural highlights
FunctionFAA28_MYCTU 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.[1] [2] [3] Publication Abstract from PubMedActivation of fatty acids as acyl-adenylates by fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis is a variant of a classical theme that involves formation of acyl-CoA (coenzyme A) by fatty acyl-CoA ligases (FACLs). Here, we show that FAALs and FACLs possess similar structural fold and substrate specificity determinants, and the key difference is the absence of a unique insertion sequence in FACL13 structure. A systematic analysis shows a conserved hydrophobic anchorage of the insertion motif across several FAALs. Strikingly, mutagenesis of two phenylalanine residues, which are part of the anchorage, to alanine converts FAAL32 to FACL32. This insertion-based in silico analysis suggests the presence of FAAL homologues in several other non-mycobacterial genomes including eukaryotes. The work presented here establishes an elegant mechanism wherein an insertion sequence drives the functional divergence of FAALs from canonical FACLs. Molecular Basis of the Functional Divergence of Fatty Acyl-AMP Ligase Biosynthetic Enzymes of Mycobacterium tuberculosis.,Goyal A, Verma P, Anandhakrishnan M, Gokhale RS, Sankaranarayanan R J Mol Biol. 2011 Dec 21. PMID:22206988[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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