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151.
Disulphide bridges involving juxtaposed half-cystines are observed in a number of protein three-dimensional structures analyzed from the Protein Data Bank. These disulphide bridges comprise a 'ring of 8-atoms' corresponding to Calpha1-C'-N-Calpha2-Cbeta2-Sgamma2-Sgamma1-Cbeta1-Calpha1 in the two half-cystines. The presence of such disulphide bridges introduces a 'bend' or 'kink' in the protein polypeptide chain. 相似文献
152.
Microevolution of cytochrome bd oxidase in Staphylococci and its implication in resistance to respiratory toxins released by Pseudomonas 下载免费PDF全文
Voggu L Schlag S Biswas R Rosenstein R Rausch C Götz F 《Journal of bacteriology》2006,188(23):8079-8086
Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic pathogens and frequently coinfect the lungs of cystic fibrosis patients. P. aeruginosa secretes an arsenal of small respiratory inhibitors, like pyocyanin, hydrogen cyanide, or quinoline N-oxides, that may act against the commensal flora as well as host cells. Here, we show that with respect to their susceptibility to these respiratory inhibitors, staphylococcal species can be divided into two groups: the sensitive group, comprised of pathogenic species such as S. aureus and S. epidermidis, and the resistant group, represented by nonpathogenic species such as S. carnosus, S. piscifermentans, and S. gallinarum. The resistance in the latter group of species was due to cydAB genes that encode a pyocyanin- and cyanide-insensitive cytochrome bd quinol oxidase. By exchanging cydB in S. aureus with the S. carnosus-specific cydB, we could demonstrate that CydB determines resistance. The resistant or sensitive phenotype was based on structural alterations in CydB, which is part of CydAB, the cytochrome bd quinol oxidase. CydB represents a prime example of both microevolution and the asymmetric pattern of evolutionary change. 相似文献
153.
Thiagarajan Madheswaran Rengarajan Baskaran Chul Soon Yong Bong Kyu Yoo 《AAPS PharmSciTech》2014,15(1):44-51
The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1–208.6 and 153.7–243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm−2h−1) compared with lower concentration (0.029 ± 0.007 μgcm−2h−1). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.KEY WORDS: Cremophor, finasteride, liquid crystalline nanoparticles, skin permeation–retention 相似文献
154.
Photonic modulation of epidermal growth factor receptor halts receptor activation and cancer cell migration 下载免费PDF全文
Cláudia M. Botelho Odete Gonçalves Rogério Marques Viruthachalam Thiagarajan Henrik Vorum Andreia C. Gomes Maria Teresa Neves‐Petersen 《Journal of biophotonics》2018,11(9)
Epidermal growth factor receptor (EGFR) plays a key role in regulating cell survival, proliferation and migration, and its overexpression and activation has been correlated with cancer progression. Cancer therapies targeting EGFR have been applied in the clinic with some success. We show, by confocal microscopy analysis, that illumination of adenocarcinomic human alveolar basal epithelial cells (Human A549—EGFR biosensor cell line) with 280 nm at irradiance levels up to 20 times weaker than the Ultraviolet B (UVB) solar output for short periods of time (15‐45 minutes) prevents epidermal growth factor‐mediated activation of EGFR located on the cell membrane, preventing or reducing cellular disaggregation, formation of filopodia and cell migration. This effect of Ultraviolet (UV) light illumination was confirmed further in a functional scratch assay, and shown to be more effective than that of a specific EGFR‐signaling inhibitor. This new photonic approach may be applicable to the treatment of various types of cancer, alone or in combination with other therapies. 相似文献
155.
Balaji Prakash M. R. N. Murthy Y. N. Sreerama D. Rajagopal Rao Lalitha R. Gowda 《Journal of biosciences》1997,22(5):545-554
Bowman-Birk inhibitors (BBI) isolated from plant seeds are small proteins active against trypsin and/or chymotrypsin. These
inhibitors have been extensively studied in terms of their structure, interactions, function and evolution. Examination of
the known three-dimensional structures of BBIs revealed similarities and subtle differences. The hydrophobic core, deduced
from surface accessibility and hydrophobicity plots, corresponding to the two tandem structural domains of the double headed
BBI are related by an almost exact two-fold, in contrast to the reactive site loops which depart appreciably from the two-fold
symmetry. Also, the orientations of inhibitory loops in soybean and peanut inhibitors were different with respect to the rigid
core. Based on the structure of Adzuki bean BBI-trypsin complex, models of trypsin and chymotryspin bound to the monomeric
soybean BBI (SBI) were constructed. There were minor short contacts between the two enzymes bound to the inhibitor suggesting
near independence of binding. Binding studies revealed that the inhibition of one enzyme in the presence of the other is associated
with a minor negative cooperativity. In order to assess the functional significance of the reported oligomeric forms of BBI,
binding of proteases to the crystallographic and non-crystallographic dimers as found in the crystal structure of peanut inhibitor
were examined. It was found that all the active sites in these oligomers cannot simultaneously participate in inhibition. 相似文献
156.
157.
The availability of complete genome sequences of H. pylori 26695 has provided a wealth of information enabling us to carry out in silico studies to identify new molecular targets for pharmaceutical treatment. In order to construe the structural and functional information of complete proteome, use of computational methods are more relevant since these methods are reliable and provide a solution to the time consuming and expensive experimental methods. Out of 1590 predicted protein coding genes in H. pylori, experimentally determined structures are available for only 145 proteins in the PDB. In the absence of experimental structures, computational studies on the three dimensional (3D) structural organization would help in deciphering the protein fold, structure and active site. Functional annotation of each protein was carried out based on structural fold and binding site based ligand association. Most of these proteins are uncharacterized in this proteome and through our annotation pipeline we were able to annotate most of them. We could assign structural folds to 464 uncharacterized proteins from an initial list of 557 sequences. Of the 1195 known structural folds present in the SCOP database, 411 (34% of all known folds) are observed in the whole H. pylori 26695 proteome, with greater inclination for domains belonging to α/β class (36.63%). Top folds include P-loop containing nucleoside triphosphate hydrolases (22.6%), TIM barrel (16.7%), transmembrane helix hairpin (16.05%), alpha-alpha superhelix (11.1%) and S-adenosyl-L-methionine-dependent methyltransferases (10.7%). 相似文献
158.
159.
V. Sukhithasri N. Nisha Lalitha Biswas V. Anil Kumar Raja Biswas 《Microbiological research》2013,168(7):396-406
The innate immune system constitutes the first line of defence against invading microbes. The basis of this defence resides in the recognition of defined structural motifs of the microbes called “Microbial associated molecular patterns” that are absent in the host. Cell wall, the outer layer of both bacterial and fungal cells, a unique structure that is absent in the host and is recognized by the germ line encoded host receptors. Nucleotide oligomerization domain proteins, peptidoglycan recognition proteins and C-type lectins are host receptors that are involved in the recognition of bacterial cell wall (usually called peptidoglycan), whereas fungal cell wall components (N- and O-linked mannans, β-glucans etc.) are recognized by host receptors like C-type lectins (Dectin-1, Dectin-2, mannose receptor, DC-SIGN), Toll like receptors-2 and -4 (TLR-2 and TLR-4). These recognitions lead to activation of a variety of host signaling cascades and ultimate production of anti-microbial compounds including phospholipase A2, antimicrobial peptides, lysozyme, reactive oxygen and nitrogen species. These molecules act in cohort against the invading microbes to eradicate infections. Additionally pathogen recognition leads to the production of cytokines, which further activate the adaptive immune system. Both pathogenic and commensal bacteria and fungus use numerous strategies to subvert the host defence. These strategies include bacterial peptidoglycan glycan backbone modifications by O-acetylation, N-deacetylation, N-glycolylation and stem peptide modifications by amidation of meso-Diaminopimelic acid; fungal cell wall modifications by shielding the β-glucan layer with mannoproteins and α-1,3 glucan. This review focuses on the recent advances in understanding the role of bacterial and fungal cell wall in their innate immune recognition and evasion strategies. 相似文献
160.
Kandasamy Parameswaran Paramasivam Sivaguru Appaswami Lalitha 《Bioorganic & medicinal chemistry letters》2013,23(13):3873-3878
One pot cyclocondensation reaction of barbituric/thiobarbituric acid with aromatic aldehydes and p-phenylenediamine/2,6-diaminopyridine by refluxing in glacial acetic acid afforded novel bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-diones)/pyrido bis(pyrimido[5,4-c]quinoline-2,4(1H,3H)-diones. All the synthesized compounds were screened for their antioxidant activities using FRAP and DPPH methods. Compounds with chloro substituents showed relatively good antioxidant properties. 相似文献