Characterization of the Mycobacterial Acyl-CoA Carboxylase Holo Complexes Reveals Their Functional Expansion into Amino Acid Catabolism
Fig 7
Structural conservation of the M. tuberculosis AccD1 CT active site.
(A) Overall MCC quaternary arrangement, as determined previously for MCC from P. aeruginosa [17]. The BT subunits of the two distal trimeric tiers are shown in different green shadings. The central hexameric CT subunit assembly is shown in different colors. One dimeric CT subunit assembly in grey/cyan has been depicted in the lower panel and the CT active site formed within the dimeric interface is indicated by sphere presentation of the modeled substrate 3-methylcrotonyl-CoA with atom-specific colors (carbon, green) [17]. (B) Sequence alignment of the predicted M. tuberculosis AccD1 3-methylcrotonyl-CoA substrate-binding segment with the respective sequence segments of the P. aeruginosa MCC and M. tuberculosis AccD2 of unknown function. The residues numbers indicated refer to the AccD1 sequence. Conserved residue positions are indicated with asterisks. Residue positions that are conserved in the two upper confirmed MCC sequences (Phe151, Phe158, Phe161 in M. tuberculosis AccD1) but not in the AccD2 sequence are indicated by arrows. The complete sequence alignment is shown in S9 Fig. (C) Residues that interact with 3-methylcrotonyl-CoA in the P. aeruginosa MCC model [17], as determined with PISA [47], are shown in stick presentation and are labeled. Color codes are as in panel A. (D) Homology model of the M. tuberculosis AccD1 CT active site. Residues that are invariant in an alignment of the CT sequences from P. aeruginosa and M. tuberculosis (S9 Fig.) are in red, demonstrating a very high level of conservation of the AccD1 active site; conserved residues are in orange, non-conserved residues are in grey.