3T5B

Crystal structure of N-terminal domain of FACL13 from Mycobacterium tuberculosis

Summary for 3T5B

• Entry DOI: 10.2210/pdb3t5b/pdb
• Related: 3T5A 3T5C
• Descriptor: PROBABLE CHAIN-FATTY-ACID-CoA LIGASE FADD13 (2 entities in total)
• Functional Keywords: acetyl-coa synthetase like fold, ligase, amp-binding
• Biological source: Mycobacterium tuberculosis
• Cellular location: Cell membrane; Peripheral membrane protein: O53306
• Total number of polymer chains: 1
• Total formula weight: 42841.78

Authors

Goyal, A.,Sankaranarayanan, R. (deposition date: 2011-07-27, release date: 2012-01-25, Last modification date: 2023-11-01)

Primary citation

Goyal, A.,Verma, P.,Anandhakrishnan, M.,Gokhale, R.S.,Sankaranarayanan, R.
Molecular basis of the functional divergence of fatty acyl-AMP ligase biosynthetic enzymes of Mycobacterium tuberculosis.
J.Mol.Biol., 416:221-238, 2012

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.

PubMed: 22206988
DOI: 10.1016/j.jmb.2011.12.031

Experimental method

X-RAY DIFFRACTION (2.35 Å)