Structural highlights
Function
ACCA3_MYCTU Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit catalyzes the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain, resulting in the formation of carboxyl biotin (PubMed:16354663, PubMed:16385038, PubMed:17114269). When associated with the beta5 subunit AccD5, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for propionyl-CoA (PubMed:16354663, PubMed:16385038). When associated with the beta6 subunit AccD6, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for acetyl-CoA (PubMed:17114269). When associated with the beta4 subunit AccD4, the beta5 subunit AccD5 and the epsilon subunit AccE5, forms the LCC complex, which is involved in the carboxylation of long chain acyl-CoA (PubMed:16354663, PubMed:28222482). The LCC complex can use C16-C24 substrates, the highest specific activity is obtained with carboxy-C20-CoA (PubMed:28222482).[1] [2] [3] [4]
Publication Abstract from PubMed
Biotin-dependent acetyl-CoA carboxylases catalyze the committed step in type II fatty acid biosynthesis, the main route for production of membrane phospholipids in bacteria, and are considered a key target for antibacterial drug discovery. Here we describe the first structure of AccA3, an essential component of the acetyl-CoA carboxylase system in Mycobacterium tuberculosis (MTb). The structure, sequence comparisons, and modeling of ligand-bound states reveal that the ATP cosubstrate-binding site shows distinct differences compared to other bacterial and eukaryotic biotin carboxylases, including all human homologs. This suggests the possibility to design MTb AccA3 subtype-specific inhibitors. DATABASE: Coordinates and structure factors have been deposited in the Protein Data Bank with the accession number 5MLK.
Crystal structure of the essential biotin-dependent carboxylase AccA3 from Mycobacterium tuberculosis.,Bennett M, Hogbom M FEBS Open Bio. 2017 Apr 4;7(5):620-626. doi: 10.1002/2211-5463.12212. eCollection, 2017 May. PMID:28469974[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Oh TJ, Daniel J, Kim HJ, Sirakova TD, Kolattukudy PE. Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent acyl-CoA Carboxylase in Mycobacterium tuberculosis H37Rv. J Biol Chem. 2006 Feb 17;281(7):3899-908. PMID:16354663 doi:10.1074/jbc.M511761200
- ↑ Gago G, Kurth D, Diacovich L, Tsai SC, Gramajo H. Biochemical and structural characterization of an essential acyl coenzyme A carboxylase from Mycobacterium tuberculosis. J Bacteriol. 2006 Jan;188(2):477-86. PMID:16385038 doi:10.1128/JB.188.2.477-486.2006
- ↑ Daniel J, Oh TJ, Lee CM, Kolattukudy PE. AccD6, a member of the Fas II locus, is a functional carboxyltransferase subunit of the acyl-coenzyme A carboxylase in Mycobacterium tuberculosis. J Bacteriol. 2007 Feb;189(3):911-7. doi: 10.1128/JB.01019-06. Epub 2006 Nov 17. PMID:17114269 doi:http://dx.doi.org/10.1128/JB.01019-06
- ↑ Bazet Lyonnet B, Diacovich L, Gago G, Spina L, Bardou F, Lemassu A, Quémard A, Gramajo H. Functional reconstitution of the Mycobacterium tuberculosis long-chain acyl-CoA carboxylase from multiple acyl-CoA subunits. FEBS J. 2017 Apr;284(7):1110-1125. PMID:28222482 doi:10.1111/febs.14046
- ↑ Bennett M, Hogbom M. Crystal structure of the essential biotin-dependent carboxylase AccA3 from Mycobacterium tuberculosis. FEBS Open Bio. 2017 Apr 4;7(5):620-626. doi: 10.1002/2211-5463.12212. eCollection, 2017 May. PMID:28469974 doi:http://dx.doi.org/10.1002/2211-5463.12212
