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991.
Nori Sawada Noriyuki Nagahara Tadashi Sakai Yoshiaki Nakajima Masayasu Minami Tomoyuki Kawada 《Journal of biological inorganic chemistry》2005,10(2):199-207
Human porphobilinogen synthase [EC.4.2.1.24] is a homo-octamer enzyme. In the active center of each subunit, four cysteines are titrated with 5,5-dithiobis(2-nitrobenzoic acid). Cys122, Cys124 and Cys132 are placed near two catalytic sites, Lys199 and Lys252, and coordinate a zinc ion, referred to as a proximal zinc ion, and Cys223 is placed at the orifice of the catalytic cavity and coordinates a zinc ion, referred to as a distal zinc ion, with His131 . When the wild-type enzymes C122A (Cys122Ala), C124A (Cys124Ala), C132A (Cys132Ala) and C223A (Cys223Ala) were oxidized by hydrogen peroxide, the levels of activity were decreased. Two cysteines were titrated with 5,5-dithiobis(2-nitrobenzoic acid) in the wild-type enzyme, while on the other hand, one cysteine was titrated in the mutant enzymes. When wild-type and mutant enzymes were reduced by 2-mercaptoethanol, the levels of activity were increased: four and three cysteines were titrated, respectively, suggesting that a disulfide bond was formed among Cys122, Cys124 and Cys132 under oxidizing conditions. We analyzed the enzyme-bound zinc ion of these enzymes using inductively coupled plasma mass spectrometry with gel-filtration chromatography. The results for C223A showed that the number of proximal zinc ions correlated to the level of enzymatic activity. Furthermore, zinc-ion-free 2-mercaptoethanol increased the activity of the wild-type enzyme without a change in the total number of zinc ions, but C223A was not activated. These findings suggest that a distal zinc ion moved to the proximal binding site when a disulfide bond among Cys122, Cys124 and Cys132 was reduced by reductants. Thus, in the catalytic functioning of the enzyme, the distal zinc ion does not directly contribute but serves rather as a reserve as the next proximal one that catalyzes the enzyme reaction. A redox change of the three cysteines in the active center accommodates the catch and release of the reserve distal zinc ion placed at the orifice of the catalytic cavity. 相似文献
992.
Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia 总被引:3,自引:0,他引:3 下载免费PDF全文
Nieuwenhuis E Motoyama J Barnfield PC Yoshikawa Y Zhang X Mo R Crackower MA Hui CC 《Molecular and cellular biology》2006,26(17):6609-6622
Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and vertebrates. The Patched1 (Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2(tm1/tm1) mice. Our molecular analysis suggests that Ptc2(tm1) likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2(tm1/tm1) mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2(tm1/tm1) male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis. 相似文献
993.
Crews DE Harada H Aoyagi K Maeda T Alfarano A Sone Y Kusano Y 《Journal of physiological anthropology》2012,31(1):18
ABSTRACT: BACKGROUND: Between July and September 2005, a preliminary sampling of the elderly population of Hizen-Oshima Island, Nagasaki Prefecture, Japan was conducted by the local hospital's nursing staff. RESULTS: Reported here are preliminary results from this sample of 27 individuals with an average age of 71 years. Their ages ranged from 51 to 82 years, with a standard deviation (sd) of 7.4 years. In total, 33 aspects of physical and physiological variation were assessed on these 15 women and 12 men. As expected from previous studies of Japanese elders, our sample shows slightly elevated average blood pressure (142/81 mmHg, sd 16/10), but they are relatively lean (waist/hip = .9: sd 0.06) when compared to European or American standards. However, their average total cholesterol (TC = 210 mg/dl, sd = 42.8) is high compared to standards, as is their high-density lipoprotein cholesterol (HDLc = 55.4 mg/dl, sd = 15.1). Means, standard deviations (sd), ranges, and upper bounds for quartile cut-points for all 10 variables used in the calculation of allostatic load (AL) were assessed. The overall average estimate for AL in this sample is 3.1 (sd = 1.58) and ranges from 1-7. CONCLUSION: AL shows variability across men and women, has little correlation with age, and is associated with physiological variation in blood glucose, dopamine, and uric acid. 相似文献
994.
CO2 efflux from subterranean nests of ant communities in a seasonal tropical forest,Thailand 下载免费PDF全文
Sasitorn Hasin Mizue Ohashi Akinori Yamada Yoshiaki Hashimoto Wattanachai Tasen Tomonori Kume Seiki Yamane 《Ecology and evolution》2014,4(20):3929-3939
Many ant species construct subterranean nests. The presence of their nests may explain soil respiration “hot spots”, an important factor in the high CO2 efflux from tropical forests. However, no studies have directly measured CO2 efflux from ant nests. We established 61 experimental plots containing 13 subterranean ant species to evaluate the CO2 efflux from subterranean ant nests in a tropical seasonal forest, Thailand. We examined differences in nest CO2 efflux among ant species. We determined the effects of environmental factors on nest CO2 efflux and calculated an index of nest structure. The mean CO2 efflux from nests was significantly higher than those from the surrounding soil in the wet and dry seasons. The CO2 efflux was species‐specific, showing significant differences among the 13 ant species. The soil moisture content significantly affected nest CO2 efflux, but there was no clear relationship between nest CO2 efflux and nest soil temperature. The diameter of the nest entrance hole affected CO2 efflux. However, there was no significant difference in CO2 efflux rates between single‐hole and multiple‐hole nests. Our results suggest that in a tropical forest ecosystem the increase in CO2 efflux from subterranean ant nests is caused by species‐specific activity of ants, the nest soil environment, and nest structure. 相似文献
995.
Satoshi Kume Young-Ho Lee Masatoshi Nakatsuji Yoshiaki Teraoka Keisuke Yamaguchi Yuji Goto Takashi Inui 《FEBS letters》2014
The hydrophobic cavity of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to accommodate various lipophilic ligands through hydrophobic effects, but its energetic origin remains unknown. We characterized 18 buffer-independent binding systems between human L-PGDS and lipophilic ligands using isothermal titration calorimetry. Although the classical hydrophobic effect was mostly detected, all complex formations were driven by favorable enthalpic gains. Gibbs energy changes strongly correlated with the number of hydrogen bond acceptors of ligand. Thus, the broad binding capability of L-PGDS for ligands should be viewed as hydrophilic interactions delicately tuned by enthalpy–entropy compensation using combined effects of hydrophilic and hydrophobic interactions. 相似文献
996.
997.
Shigehiro Asano Masafumi Komiya Nobuyuki Koike Erina Koga Shogo Nakatani Yoshiaki Isobe 《Bioorganic & medicinal chemistry letters》2010,20(22):6696-6698
A novel series of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines containing substituted phenyl sulfonamide are synthesized and evaluated for their inhibitory activity against CaMKII. Substituents on the phenyl group had significant impact on CaMKII inhibition, in particular, the inhibitory activity of 8p was 25-fold higher than that of KN-93, a known CaMKII inhibitor. Michaelis–Menten analysis of a representative compound suggested that the synthesized pyrimidines are calmodulin non-competitive inhibitors. Finally, 8p exhibited more than 100-fold higher selectivity for CaMKII over five types of off-target kinases. 相似文献
998.
999.
The tertiary structures and conformational dynamics of transmembrane (TM) helical proteins are maintained by the interhelical interaction network in membranes, although it is complicated to analyze the underlying driving forces because the amino acid sequences can involve multiple and various types of interactions. To obtain insights into basal and common effects of the number of membrane-spanning segments and membrane cholesterol, we measured stabilities of helix bundles composed of simple TM helices (AALALAA)3 (1TM) and (AALALAA)3-G5-(AALALAA)3 (2TM). Association–dissociation dynamics for 1TM–1TM, 1TM–2TM, and 2TM–2TM pairs were monitored to compare stabilities of 2-, 3-, and 4-helical bundles, respectively, with single-pair fluorescence resonance energy transfer (sp-FRET) in liposome membranes. Both thermodynamic and kinetic stabilities of the helix bundles increased with a greater number of membrane-spanning segments in POPC. The presence of 30 mol% cholesterol strongly enhanced the formation of 1TM–1TM and 1TM–2TM bundles (~ ? 9 kJ mol?1), whereas it only weakly stabilized the 2TM–2TM bundle (~ ? 3 kJ mol?1). Fourier transform infrared-polarized attenuated total reflection (ATR-FTIR) spectroscopy revealed an ~30° tilt of the helix axis relative to bilayer normal for the 1TM–2TM pair in the presence of cholesterol, suggesting the formation of a tilted helix bundle to release high lateral pressure at the center of cholesterol-containing membranes. These results demonstrate that the number of membrane-spanning segments affects the stability and structure of the helix bundle, and their cholesterol-dependences. Such information is useful to understand the basics of folding and assembly of multispanning TM proteins. 相似文献
1000.
Ichthyological Research - Lythrichthys Jordan and Starks 1904 (Setarchidae), previously regarded as a junior synonym of Setarches Johnson 1862, is recognized as valid, despite sharing some... 相似文献