Structural diversity in the six-fold redundant set of acyl-CoA carboxyltransferases in Mycobacterium tuberculosis

• Published in: FEBS letters Vol. 580; no. 30; pp. 6898 - 6902
• Main Authors: Holton, Simon J., King-Scott, Stephanie, Eddine, Ali Nasser, Kaufmann, Stefan H.E., Wilmanns, Matthias
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 22.12.2006
• Subjects: ACC; ACCase; acetyl-CoA transferase; Acyl Coenzyme A - metabolism; Acyl-CoA carboxylase; BCCP; Binding Sites; biotin carboxylase; biotin carrier protein; Carboxyl and Carbamoyl Transferases - chemistry; Carboxyl and Carbamoyl Transferases - genetics; Carboxyl and Carbamoyl Transferases - metabolism; carboxytransferase; Crystallography, X-Ray; Models, Molecular; Mycobaceterium tuberculosis; Mycobacterium tuberculosis; Mycobacterium tuberculosis - enzymology; Mycobacterium tuberculosis - genetics; PccB; propionyl-CoA carboxytransferase; Protein Binding; Protein complex reconstitution; Protein Folding; Protein Structure, Quaternary; Protein Subunits - genetics; Protein Subunits - metabolism; Structural proteomics; X-ray crystallography; X-ray crystallography; Protein complex reconstitution; ACC; BCCP; BC; CT; Structural proteomics; Acyl-CoA carboxylase; PccB; ACCase; Mycobaceterium tuberculosis
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.11.054

Mycobacterium tuberculosis contains multiple versions of the accA and accD genes that encode the α- and β-subunits of at least three distinct multi-functional acyl-CoA carboxylase complexes. Because of its proposed involvement in pathogenic M. tuberculosis survival, the high-resolution crystal structure of the β-subunit gene accD5 product has been determined and reveals a hexameric 356kDa complex. Analysis of the active site properties of AccD5 and homology models of the other five M. tuberculosis AccD homologues reveals unexpected differences in their surface composition, providing a molecular rational key for a sorting mechanism governing correct acyl-CoA carboxylase holo complex assembly in M. tuberculosis.