Crystal structures and mutational analyses of acyl-CoA carboxylase beta subunit of Streptomyces coelicolor.

  title={Crystal structures and mutational analyses of acyl-CoA carboxylase beta subunit of Streptomyces coelicolor.},
  author={Ana Arabolaza and Mary Elizabeth Shillito and Ting-Wan Lin and Lautaro Diacovich and M. M. Melgar and Huy Pham and Deborah L Amick and Hugo Gramajo and Shiou-Chuan Tsai},
  volume={49 34},
The first committed step of fatty acid and polyketides biosynthesis, the biotin-dependent carboxylation of an acyl-CoA, is catalyzed by acyl-CoA carboxylases (ACCases) such as acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC). ACC and PCC in Streptomyces coelicolor are homologue multisubunit complexes that can carboxylate different short chain acyl-CoAs. While ACC is able to carboxylate acetyl-, propionyl-, or butyryl-CoA with approximately the same specificity, PCC only… 
Kinetic, Structural, and Mutational Analysis of Acyl-CoA Carboxylase From Thermobifida fusca YX
Structural and kinetic analyses of an AcCCase from Thermobifida fusca YX are conducted, suggesting that residue D427 of AcCCB subunits is an important, but not sole determinant of the substrate specificity of Ac CCase enzymes.
Structure, function and selective inhibition of bacterial acetyl-coa carboxylase
Structural biology, together with small molecule inhibitor studies, has provided new insights into the molecular mechanisms that govern ACC catalysis, specifically the BC and CT subunits and the implications for early stage antibiotic discovery projects are discussed.
A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units
X-ray crystal structures of the unusual β-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.
Structure, Activity, and Inhibition of the Carboxyltransferase β-Subunit of Acetyl Coenzyme A Carboxylase (AccD6) from Mycobacterium tuberculosis
The crystal structures of M. tuberculosis AccD6 show the potential for developing novel therapeutics for tuberculosis based on herbicides with low human toxicity, and two molecules of the inhibitor bound on each AccD 6 subunit are reported.
Structural and Functional Studies on Acyl-CoA Carboxylases of Mycobacterium tuberculosis
X-ray crystallography and complementary biophysical and biochemical approaches have been employed in an attempt to address questions concerning interactions between YCC components and differences in beta subunit substrate specificity, which have added to the existing knowledge of the M. tuberculosis structural proteome.
Structure and function of biotin-dependent carboxylases
  • L. Tong
  • Biology, Chemistry
    Cellular and Molecular Life Sciences
  • 2012
Understanding ofiotin-dependent carboxylases has been greatly enhanced over the past few years by the crystal structures of the holoenzymes of PCC, MCC, PC, and UC, which provide a molecular basis for understanding their catalytic mechanism as well as the large collection of disease-causing mutations.
AccR, a TetR Family Transcriptional Repressor, Coordinates Short-Chain Acyl Coenzyme A Homeostasis in Streptomyces avermitilis
A TetR family transcriptional repressor, AccR, is characterized that mediates intracellular acetyl-, propionyl-, methylcrotonyl-, malonyl-, and methylmalonyl-CoA levels by controlling the transcription of genes that encode the main ACCase and enzymes associated with branched-chain amino acid metabolism in Streptomyces.
Early evolution of the biotin-dependent carboxylase family
The phylogenetic analyses support previous suggestions about the existence of an ancient bifunctional biotin-protein ligase bound to a regulatory transcription factor in the cenancestor of all living organisms.