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Molecular Basis of the Functional Divergence of Fatty Acyl-AMP Ligase Biosynthetic Enzymes of Mycobacterium tuberculosis
- Source :
-
Journal of Molecular Biology . Feb2012, Vol. 416 Issue 2, p221-238. 18p. - Publication Year :
- 2012
-
Abstract
- Abstract: Activation 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00222836
- Volume :
- 416
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular Biology
- Publication Type :
- Academic Journal
- Accession number :
- 71339401
- Full Text :
- https://doi.org/10.1016/j.jmb.2011.12.031