3T5A

Molecular basis of the functional divergence of fatty acyl-AMP ligase biosynthetic enzymes of Mycobacterium tuberculosis.

(2012) J Mol Biol 416: 221-238

• PubMed: 22206988 Search on PubMed
• DOI: https://doi.org/10.1016/j.jmb.2011.12.031
• Primary Citation of Related Structures:  
  3T5A, 3T5B, 3T5C


• PubMed 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.

   View More

---

Organizational Affiliation: 

Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Hyderabad 500 007, India.