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1.  Acyl-Coenzyme A:cholesterol Acyltransferase 1: Significance of Single Nucleotide Polymorphism at Residue 526 and Role of Proline 347 near the Fifth Transmembrane Domain 
The FEBS journal  2014;281(7):1773-1783.
Acyl-Coenzyme A:cholesterol Acyltransferases (ACATs), members of the membrane bound O-acyltransferase (MBOAT) family, catalyze the conversion of cholesterol to cholesteryl esters. Mammals contain two isoenzymes ACAT1 and ACAT2. Both enzymes are drug targets for treating human diseases. ACAT1 is present ubiquitously in various cell types. It contains 9 transmembrane domains (TMDs) with the active site H460 locating within TMD #7, and another active site N421 locating within the 4th large cytoplasmic loop. In human ACAT1, a single nucleotide polymorphism (SNP) exists for residue 526: the codon is either CAG for glutamine (Q), or CGG for arginine (R). Q/R 526 is present within the Cterminal loop. Its biochemical significance is unknown. In addition, within the Cterminal half of ACAT1, numerous residues conserved with those of ACAT2 are present; the functions of these conserved residues are largely unknown. Here we performed single substitution mutagenesis experiments to investigate the roles of individual residues present in the C-terminal loop including Q/R526, and the 8 conserved prolines (P) located near/at various TMDs. The results show that the enzyme activity of ACAT1 Q526 is less active than that of ACAT1 R526 by 40%. In addition, several residues in the C-terminal loop are important to maintain proper ACAT1 protein stability. Other results show that the P347 plays important role in modulating enzyme catalysis. Overall, our results implicate that the CAG/CGG polymorphism can be utilized to perform ACAT1 activity/human disease susceptibility studies, and that P347 located near TMD #5 plays an important role in modulating enzyme catalysis.
PMCID: PMC4060832  PMID: 24517390
Single nucleotide polymorphism; Cholesterol metabolism; Atherosclerosis; Alzheimer’s disease; Site-specific mutagenesis
2.  Adsorption structure of dimethyl ether on silicalite-1 zeolite determined using single-crystal X-ray diffraction 
The most stable sorption site of dimethyl ether on silicalite-1 is the sinusoidal channel. The configuration of guest molecules (linear or bent) plays an important role in determining where the stable sorption site is situated.
The adsorption structures of dimethyl ether (DME) on silicalite-1 zeolite (MFI-type) are determined using single-crystal X-ray diffraction. The structure of low-loaded DME-silicalite-1 indicates that all DME molecules are located in the sinusoidal channel, which is the most stable sorption site based on the van der Waals interaction between DME and the framework. The configuration of guest molecules (linear or bent) plays an important role in determining where the stable sorption site is in the pore system of MFI-type zeolites. Bent molecules favor the sinusoidal channel, while linear molecules favor the straight channel. The contribution of DME–DME interactions is considerable in the high-loaded DME-silicalite-1 structure.
PMCID: PMC4184374  PMID: 25274519
adsorption structure; MFI-type zeolite; silicalite-1; dimethyl ether; single-crystal structure analysis
3.  Final storage of radioactive cesium by pollucite hydrothermal synthesis 
Scientific Reports  2014;4:4195.
The Fukushima nuclear accident has highlighted the importance of finding a better final storage method for radioactive cesium species. Cs is highly soluble in water, and can easily exchange with other alkali ions in zeolites or clays to form stable complexes. However, Cs+ is released from Cs+ complexes into water when surrounded by an excess of water. Pollucite may be the best final storage option for Cs+, but its typical synthesis requires heating to about 1200°C in air. Here, we show that the hydrothermal synthesis of pollucite can be completed at 300°C in three hours from any zeolite or clay. Furthermore, our procedure does not require ion exchange before synthesis. Radioactive Cs is usually found in complexes with clays. At that time, this method only requires calcium hydroxide, water, and three hours of hydrothermal synthesis, so the process is both inexpensive and practical for large-scale application. Pollucite is an analog of analcime zeolite, and contains a channel system 2.8 Å in diameter, which is formed by 6-oxygen rings. As the diameter of Cs+ is 3.34 Å and each Cs+ exists independently within a separate portion of the channel, Cs+ cannot exit the pollucite framework without breaking it.
PMCID: PMC3935194  PMID: 24569302
4.  Involvement of Reactive Oxygen Species in Sonodynamically Induced Apoptosis Using a Novel Porphyrin Derivative 
Theranostics  2012;2(9):880-888.
In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I), and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique. Cells treated with 8 μM DCPH-P-Na(I) and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or DCPH-P-Na(I) alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and DCPH-P-Na(I) but not in cells treated with ultrasound or DCPH-P-Na(I) alone. In addition, the combination of DCPH-P-Na(I) and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and DCPH-P-Na(I) induced apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. These experimental results support the possibility of sonodynamic treatment for cancer using the induction of apoptosis.
PMCID: PMC3475214  PMID: 23082100
Apoptosis; Sonodynamic therapy; Ultrasound; DCPH-P-Na(I); HL-60 cells, Reactive Oxygen, Caspase-3.
5.  Determining the structure of a benzene7.2-silicalite-1 zeolite using a single-crystal X-ray method 
An orthorhombic benzene-silicalite-1 single crystal was obtained from a monoclinic twin crystal, and the structure was determined by a single-crystal method for the first time.
A simple method for preparing orthorhombic single crystals of benzene-silicalite-1 was developed. A silicalite-1 crystal was pressed with a weight of 2 g along the +c and −c crystallographic axes while the temperature was increased to 473 K. The temperature was then slowly reduced to 313 K, and these heating and cooling steps were repeated three times. After the orthorhombic single crystals adsorbed benzene, the crystal structure of the resulting benzene-silicalite-1 was determined. There were two kinds of benzene molecules in the asymmetric unit. One was located at the intersection of the straight channels and the sinusoidal channels with the benzene ring parallel to the ac plane. The other benzene was located in the middle of the straight channel.
PMCID: PMC3222141  PMID: 22101540
ZSM-5; MFI; silicalite-1; benzene-silicalite-1

Results 1-5 (5)