Structure and function of animal fatty acid synthase

Fatty acid synthase (FAS; EC 2.3.1.85) of animal tissues is a complex multifunctional enzyme consisting of two identical monomers. The FAS monomer (approximately 270 kDa) contains six catalytic activities and from the N-terminus the order is beta-ketoacyl synthase (KS), acetyl/malonyl transacylase (AT/MT), beta-hydroxyacyl dehydratase (DH), enoyl reductase (ER), beta-ketoacyl reductase (KR), acyl carrier protein (ACP), and thioesterase (TE). Although the FAS monomer contains all the activities needed for palmitate synthesis, only the dimer form of the synthase is functional. Both the biochemical analyses and the small-angle neutron-scattering analysis determined that in the dimer form of the enzyme the monomers are arranged in a head-to-tail manner generating two centers for palmitate synthesis. Further, these analyses also suggested that the component activities of the monomer are organized in three domains. Domain I contains KS, AT/MT, and DH, domain II contains ER, KR, and ACP, and domain III contains TE. Approximately one fourth of the monomer protein located between domains I and II contains no catalytic activities and is called the interdomain/core region. This region plays an important role in the dimer formation. Electron cryomicrographic analyses of FAS revealed a quaternary structure at approximately 19 A resolution, containing two monomers (180 x 130 x 75 A) that are separated by about 19 A, and arranged in an antiparallel fashion, which is consistent with biochemical and neutron-scattering data. The monomers are connected at the middle by a hinge generating two clefts that may be the two active centers of fatty acid synthesis. Normal mode analysis predicted that the intersubunit hinge region and the intrasubunit hinge located between domains II and III are highly flexible. Analysis of FAS particle images by using a simultaneous multiple model single particle refinement method confirmed that FAS structure exists in various conformational states. Attempts to get higher resolution of the structure are under way.     

Identification of thyroid hormone response elements in the human fatty acid synthase promoter

To investigate the regulation of the human fatty acid synthase gene by the thyroid hormone triiodothyronine, various constructs of the human fatty acid synthase promoter and the luciferase reporter gene were transfected in combination with plasmids expressing the thyroid hormone and the retinoid X receptors in HepG2 cells. The reporter gene was activated 25-fold by the thyroid hormone in the presence of the thyroid hormone receptor. When both the thyroid hormone and the retinoid X receptors were expressed in HepG2 cells, there was about a 100-fold increase in reporter gene expression. 5'-Deletion analysis disclosed two thyroid hormone response elements, TRE1 (nucleotides -870 to -650) and TRE2 (nucleotides -272 to -40), in the human fatty acid synthase promoter. The presence of thyroid hormone response elements in these two regions of the promoter was confirmed by cloning various fragments of these two regions in the minimal thymidine kinase promoter-luciferase reporter gene plasmid construct and determining reporter gene expression. The results of this cloning procedure and those of electrophoretic mobility shift assays indicated that the sequence GGGTTAcgtcCGGTCA (nucleotides -716 to -731) represents TRE1 and that the sequence GGGTCC (nucleotides -117 to -112) represents TRE2. The sequence of TRE1 is very similar to the consensus sequence of the thyroid hormone response element, whereas the sequence of TRE2 contains only a half-site of the thyroid hormone response element consensus motif because it lacks the direct repeat. The sequences on either side of TRE2 seem to influence its response to the thyroid hormone and retinoid X receptors.     

A novel CMOS hairpin resonator using slow-wave structure

A novel hairpin resonator incorporating a defective uniplanar compact photonic bandgap (D-UCPBG) slow-wave structure has been developed using monolithic silicon-based CMOS technology and the impact of the D-UCPBG slow wave feature on the hairpin resonator performance is presented. Two stepped impedance hairpin resonators of equal dimensions, one with a solid ground plane and another with a D-UCPBG structure, were implemented in the TSMC 0.25 /spl mu/m RF-mixed signal fabrication process. The D-UCPBG incorporated hairpin resonator resonates at 4.5 GHz, a significant frequency reduction from 10.2 GHz, the resonant frequency of the solid ground plane based hairpin resonator. The loaded Q of the resonator also increases from 5.8 for the solid ground plane resonator to 13 for the D-UCPBG structure.     

DC-20 GHz CMOS LNA using novel multilayered transmission lines and inductors

A distributed low-noise amplifier (LNA) employing novel multilayered transmission lines and inductors is designed in a standard 0.18 mum CMOS process. The new LNA provides significant improvement in performance and size with less than 13 dB return loss from DC to 17 GHz, average gain of 8plusmn0.2 dB from DC to 20 GHz, noise figure of 3.4-5 dB from 0.5-19 GHz, power consumption of 34.2 mW, and 1.05times0.37 mm ² chip size including RF pads