Acetyl-CoA carboxylase (ACC) and propionyl-CoA carboxylase (PCC) catalyze the carboxylation of acetyl- and propionyl-CoA to generate malonyl- and methylmalonyl-CoA, respectively. Understanding the substrate specificity of ACC and PCC will (1) help in the development of novel structure-based inhibitors that are potential therapeutics against obesity, cancer, and infectious disease and (2) facilitate bioengineering to provide novel extender units for polyketide biosynthesis. ACC and PCC in Streptomyces coelicolor are multisubunit complexes. The core catalytic beta-subunits, PccB and AccB, are 360 kDa homohexamers, catalyzing the transcarboxylation between biotin and acyl-CoAs. Apo and substrate-bound crystal structures of PccB hexamers were determined to 2.0-2.8 A. The hexamer assembly forms a ring-shaped complex. The hydrophobic, highly conserved biotin-binding pocket was identified for the first time. Biotin and propionyl-CoA bind perpendicular to each other in the active site, where two oxyanion holes were identified. N1 of biotin is proposed to be the active site base. Structure-based mutagenesis at a single residue of PccB and AccB allowed interconversion of the substrate specificity of ACC and PCC. The di-domain, dimeric interaction is crucial for enzyme catalysis, stability, and substrate specificity; these features are also highly conserved among biotin-dependent carboxyltransferases. Our findings enable bioengineering of the acyl-CoA carboxylase (ACCase) substrate specificity to provide novel extender units for the combinatorial biosynthesis of polyketides.
We present the first detailed kinematical analysis of the planetary nebula Abell 63, which is known to contain the eclipsing close‐binary nucleus UU Sge. Abell 63 provides an important test case in investigating the role of close‐binary central stars on the evolution of planetary nebulae. Longslit observations were obtained using the Manchester echelle spectrometer combined with the 2.1‐m San Pedro Martir Telescope. The spectra reveal that the central bright rim of Abell 63 has a tube‐like structure. A deep image shows collimated lobes extending from the nebula, which are shown to be high‐velocity outflows. The kinematic ages of the nebular rim and the extended lobes are calculated to be 8400 ± 500 and 12 900 ± 2800 yr, respectively, which suggests that the lobes were formed at an earlier stage than the nebular rim. This is consistent with expectations that disc‐generated jets form immediately after the common envelope phase. A morphological–kinematical model of the central nebula is presented and the best‐fitting model is found to have the same inclination as the orbital plane of the central binary system; this is the first proof that a close‐binary system directly affects the shaping of its nebula. A Hubble‐type flow is well‐established in the morphological–kinematical modelling of the observed line profiles and imagery. Two possible formation models for the elongated lobes of Abell 63 are considered, (i) a low‐density, pressure‐driven jet excavates a cavity in the remnant asymptotic giant branch (AGB) envelope; (ii) high‐density bullets form the lobes in a single ballistic ejection event.
We present the first detailed spatiokinematical analysis and modelling of the planetary nebula Abell 41, which is known to contain the well‐studied close‐binary system MT Ser. This object represents an important test case in the study of the evolution of planetary nebulae with binary central stars as current evolutionary theories predict that the binary plane should be aligned perpendicular to the symmetry axis of the nebula. Deep narrow‐band imaging in the light of [N ii] 6584 Å, [O iii] 5007 Å and [S ii] 6717+6731 Å, obtained using ACAM on the William Herschel Telescope, has been used to investigate the ionization structure of Abell 41. Long‐slit observations of the Hα and [N ii] 6584 Å emission were obtained using the Manchester Echelle Spectrometer on the 2.1‐m San Pedro Mártir Telescope. These spectra, combined with the narrow‐band imagery, were used to develop a spatiokinematical model of [N ii] 6584 Å emission from Abell 41. The best‐fitting model reveals Abell 41 to have a waisted, bipolar structure with an expansion velocity of ∼40 km s−1 at the waist. The symmetry axis of the model nebula is within 5° of perpendicular to the orbital plane of the central binary system. This provides strong evidence that the close‐binary system, MT Ser, has directly affected the shaping of its nebula, Abell 41. Although the theoretical link between bipolar planetary nebulae and binary central stars is long established, this nebula is only the second to have this link, between nebular symmetry axis and binary plane, proved observationally.
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