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81.
Jason Z. Vlahakis Maaike Hum Mona N. Rahman Zongchao Jia Kanji Nakatsu Walter A. Szarek 《Bioorganic & medicinal chemistry》2009,17(6):2461-2475
Several imidazole–dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include a series of substituted thiophenol and substituted phenol derivatives of (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride (3), in addition to smaller functionalized derivatives, continue our structure–activity studies by exploration of the aminothiophenol region (‘northeastern region’) in our original target structure azalanstat (1). In vitro, most of the compounds in this series were found to be highly potent inhibitors of the stress-induced isozyme HO-1 and the constitutive isozyme HO-2, showing only moderate selectivity for HO-1. Nevertheless, a few of the compounds displayed higher selectivity toward HO-1. None of the compounds having a larger appendage in the northeastern region were inhibitors of CYP2E1, whereas a compound having a relatively small fluorine substituent in this region did inhibit CYP2E1; all of the compounds tested exhibited high inhibitory potency against CYP3A1/3A2. 相似文献
82.
Sato Y Shibata H Nakatsu T Nakano H Kashiwayama Y Imanaka T Kato H 《The EMBO journal》2010,29(24):4083-4093
Peroxisomes require peroxin (Pex) proteins for their biogenesis. The interaction between Pex3p, which resides on the peroxisomal membrane, and Pex19p, which resides in the cytosol, is crucial for peroxisome formation and the post-translational targeting of peroxisomal membrane proteins (PMPs). It is not known how Pex3p promotes the specific interaction with Pex19p for the purpose of PMP translocation. Here, we present the three-dimensional structure of the complex between a cytosolic domain of Pex3p and the binding-region peptide of Pex19p. The overall shape of Pex3p is a prolate spheroid with a novel fold, the 'twisted six-helix bundle.' The Pex19p-binding site is at an apex of the Pex3p spheroid. A 16-residue region of the Pex19p peptide forms an α-helix and makes a contact with Pex3p; this helix is disordered in the unbound state. The Pex19p peptide contains a characteristic motif, consisting of the leucine triad (Leu18, Leu21, Leu22), and Phe29, which are critical for the Pex3p binding and peroxisome biogenesis. 相似文献
83.
Ida C Helmark Ulla R Mikkelsen Jens Børglum Anders Rothe Marie CH Petersen Ove Andersen Henning Langberg Michael Kjaer 《Arthritis research & therapy》2010,12(4):R126-11
Introduction
The microdialysis method was applied to the human knee joint with osteoarthritis (OA) in order to reveal changes in biochemical markers of cartilage and inflammation, intraarticularly and in the synovium, in response to a single bout of mechanical joint loading. 相似文献84.
The discovery of green fluorescent protein (GFP) from jellyfish Aequorea victoria has provoked numerous studies to unveil the myriads of biomedical applications. Consequently, several studies also revealed the prevalence of fluorescence in different marine and terrestrial organisms. However, since GFP's discovery or the Nobel prize award on GFP, the fluorescence has not been explored so far from India. The current study presents the widespread fluorescent organisms resources available in India for biomedical and toxicological applications. Fluorescence emission from different plant and animal components were examined by direct observations using UV torchlight. Investigation revealed that blue light excited fluorescence in several organisms. For the first time, this study observed GFP like fluorescence in many terretrial and marine organisms of India. Observations are indicating that fluorescent proteins have essential ecological functions that are yet to be determined. The examined plant and animal components were not bioluminescent. In comparison, the potential untouched research areas on fluorescence aspects are detailed. A thorough review of fluorescent organisms reported hitherto is also provided to spread the current knowledge on fluorescence. 相似文献
85.
Keita Matsuoka Toru Nakatsu Hiroaki Kato 《Protein science : a publication of the Protein Society》2021,30(5):1064
CmABCB1 is a homologue of human P‐glycoprotein, which extrudes various substrates by iterative cycles of conformational changes between the inward‐ and outward‐facing states. Comparison of the inward‐ and outward‐facing structures of CmABCB1 suggested that pivotal joints in the transmembrane domain regulate the tilt of transmembrane helices. Transmembrane helix 1 (TM1) forms a tight helix–helix contact with TM3 at the TM1–3 joint. Mutation of Gly132 to valine at the TM1–3 joint, G132V, caused a 10‐fold increase in ATPase activity, but the mechanism underlying this change remains unclear. Here, we report a crystal structure of the outward‐facing state of the CmABCB1 G132V mutant at a 2.15 Å resolution. We observed structural displacements between the outward‐facing states of G132V and the previous one at the region around the TM1–3 joint, and a significant expansion at the extracellular gate. We hypothesize that steric hindrance caused by the Val substitution shifted the conformational equilibrium toward the outward‐facing state, favoring the dimeric state of the nucleotide‐binding domains and thereby increasing the ATPase activity of the G132V mutant. 相似文献
86.
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88.
Detection and enumeration of aromatic oxygenase genes by multiplex and real-time PCR 总被引:8,自引:0,他引:8
Our abilities to detect and enumerate pollutant-biodegrading microorganisms in the environment are rapidly advancing with the development of molecular genetic techniques. Techniques based on multiplex and real-time PCR amplification of aromatic oxygenase genes were developed to detect and quantify aromatic catabolic pathways, respectively. PCR primer sets were identified for the large subunits of aromatic oxygenases from alignments of known gene sequences and tested with genetically well-characterized strains. In all, primer sets which allowed amplification of naphthalene dioxygenase, biphenyl dioxygenase, toluene dioxygenase, xylene monooxygenase, phenol monooxygenase, and ring-hydroxylating toluene monooxygenase genes were identified. For each primer set, the length of the observed amplification product matched the length predicted from published sequences, and specificity was confirmed by hybridization. Primer sets were grouped according to the annealing temperature for multiplex PCR permitting simultaneous detection of various genotypes responsible for aromatic hydrocarbon biodegradation. Real-time PCR using SYBR green I was employed with the individual primer sets to determine the gene copy number. Optimum polymerization temperatures for real-time PCR were determined on the basis of the observed melting temperatures of the desired products. When a polymerization temperature of 4 to 5 degrees C below the melting temperature was used, background fluorescence signals were greatly reduced, allowing detection limits of 2 x 10(2) copies per reaction mixture. Improved in situ microbial characterization will provide more accurate assessment of pollutant biodegradation, enhance studies of the ecology of contaminated sites, and facilitate assessment of the impact of remediation technologies on indigenous microbial populations. 相似文献
89.
An extracellular source of heme can induce a significant heme oxygenase mediated relaxation in the rat aorta 总被引:2,自引:0,他引:2
Hosein S Marks GS Brien JF McLaughlin BE Nakatsu K 《Canadian journal of physiology and pharmacology》2002,80(8):761-765
Carbon monoxide has been under active investigation for a role in controlling vascular tone throughout the last decade because of its ability to induce relaxation in blood vessels. The underlying mechanisms of this response are hypothesized to be mediated by soluble guanylyl cyclase (sGC) and, in some instances, KCa channels. The major source of CO in major blood vessels is the catabolic process of heme degradation, which is catalyzed by heme oxygenase (HO). This heme substrate could be derived from heme sources within vascular smooth muscle cells, such as heme proteins, or by uptake from the extracellular milieu. The current study shows that the isolated rat aorta relaxes upon exposure to pharmacological concentrations of heme in the bathing medium. This response was inhibited by an inhibitor of HO (tin protoporphyrin) and sGC (1-H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one). These observations were interpreted to mean that vascular smooth muscle cells are capable of taking up and utilizing heme for the production of CO. 相似文献
90.