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111.
Studies aiming to explore the involvement of host genetic factors to determine susceptibility to develop disease and individual's response to the infection with Mycobacterium leprae have increased in recent years. To address this issue, we have developed a Leprosy Susceptible Human Gene Database (LSHGD) to integrate leprosy and human associated 45 genes by profound literature search. This will serve as a user-friendly and interactive platform to understand the involvement of human polymorphisms (SNPs) in leprosy, independent genetic control over both susceptibility to leprosy and its association with multi-drug resistance of M. leprae. As the first human genetic database in leprosy it aims to provide information about the associated genes, corresponding protein sequences, available three dimensional structures and polymorphism related to leprosy. In conclusion, this will serve as a multifunctional valuable tool and convenient information platform which is freely available at http://www.vit.ac.in/leprosy/leprosy.htm and enables the user to retrieve information of their interest. 相似文献
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Vaidehi N Schlyer S Trabanino RJ Floriano WB Abrol R Sharma S Kochanny M Koovakat S Dunning L Liang M Fox JM de Mendonça FL Pease JE Goddard WA Horuk R 《The Journal of biological chemistry》2006,281(37):27613-27620
A major challenge in the application of structure-based drug design methods to proteins belonging to the superfamily of G protein-coupled receptors (GPCRs) is the paucity of structural information (1). The 19 chemokine receptors, belonging to the Class A family of GPCRs, are important drug targets not only for autoimmune diseases like multiple sclerosis but also for the blockade of human immunodeficiency virus type 1 entry (2). Using the MembStruk computational method (3), we predicted the three-dimensional structure of the human CCR1 receptor. In addition, we predicted the binding site of the small molecule CCR1 antagonist BX 471, which is currently in Phase II clinical trials (4). Based on the predicted antagonist binding site we designed 17 point mutants of CCR1 to validate the predictions. Subsequent competitive ligand binding and chemotaxis experiments with these mutants gave an excellent correlation to these predictions. In particular, we find that Tyr-113 and Tyr-114 on transmembrane domain 3 and Ile-259 on transmembrane 6 contribute significantly to the binding of BX 471. Finally, we used the predicted and validated structure of CCR1 in a virtual screening validation of the Maybridge data base, seeded with selective CCR1 antagonists. The screen identified 63% of CCR1 antagonists in the top 5% of the hits. Our results indicate that rational drug design for GPCR targets is a feasible approach. 相似文献
114.
Nicolini C Kraineva J Khurana M Periasamy N Funari SS Winter R 《Biochimica et biophysica acta》2006,1758(2):248-258
We report on the effects of temperature and pressure on the structure, conformation and phase behavior of aqueous dispersions of the model lipid "raft" mixture palmitoyloleoylphosphatidylcholine (POPC)/bovine brain sphingomyelin (SM)/cholesterol (Chol) (1:1:1). We investigated interchain interactions, hydrogen bonding, conformational and structural properties as well as phase transformations of this system using Fourier transform-infrared (FT-IR) spectroscopy, small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) coupled with pressure perturbation calorimetry (PPC), and Laurdan fluorescence spectroscopy. The IR spectral parameters in combination with the scattering patterns from the SAXS measurements were used to detect structural and conformational transformations upon changes of pressure up to 7-9 kbar and temperature in the range from 1 to about 80 degrees C. The generalized polarization function (GP) values, obtained from the Laurdan fluorescence spectroscopy studies also reveal temperature and pressure dependent phase changes. DSC and PPC were used to detect thermodynamic properties accompanying the temperature-dependent phase changes. In combination with literature fluorescence spectroscopy and microscopy data, a tentative p,T stability diagram of the mixture has been established. The data reveal a broad liquid-order/solid-ordered (lo+so) two-phase coexistence region below 8+/-2 degrees C at ambient pressure. With increasing temperature, a lo+ld+so three-phase region is formed, which extends up to approximately 27 degrees C, where a liquid-ordered/liquid-disordered (lo+ld) immiscibility region is formed. Finally, above 48+/-2 degrees C, the POPC/SM/Chol (1:1:1) mixture becomes completely fluid-like (liquid-disordered, ld). With increasing pressure, all phase transition lines shift to higher temperatures. Notably, the lo+ld (+so) phase coexistence region, mimicking raft-like lateral phase separation in natural membranes, extends over a rather wide temperature range of about 40 degrees C, and a pressure range, which extends up to about 2 kbar for T=37 degrees C. Interestingly, in this pressure range, ceasing of membrane protein function in natural membrane environments has been observed for a variety of systems. 相似文献
115.
Lucas LH Ersoy BA Kueltzo LA Joshi SB Brandau DT Thyagarajapuram N Peek LJ Middaugh CR 《Protein science : a publication of the Protein Society》2006,15(10):2228-2243
We describe an alternate approach for studying protein structure using the detection of ultraviolet (UV) absorbance peak shifts of aromatic amino acid side chains induced by the presence of salts. The method is based on the hypothesis that salt cations (Li+, Na+, and Cs+) of varying sizes can differentially diffuse through protein matrices and interact with benzyl, phenyl, and indole groups through cation-pi interactions. We have investigated the potential of this method to probe protein dynamics by measuring high resolution second-derivative UV spectra as a function of salt concentration for eight proteins of varying physical and chemical properties and the N-acetylated C-ethyl esterified amino acids to represent totally exposed side chains. We show that small shifts in the wavelength maxima for Phe, Tyr, and Trp in the presence of high salt concentrations can be reliably measured and that the magnitude and direction of the peak shifts are influenced by several factors, including protein size, charge, and the local environment and solvent accessibility of the aromatic groups. Evaluating the empirical UV spectral data in light of known protein structural information shows that probing cation-pi interactions in proteins reveals unique information about the influence of structure on aromatic side chain spectroscopic behavior. 相似文献
116.
Biodegradation of aromatic compounds: current status and opportunities for biomolecular approaches 总被引:1,自引:0,他引:1
Biodegradation can achieve complete and cost-effective elimination of aromatic pollutants through harnessing diverse microbial
metabolic processes. Aromatics biodegradation plays an important role in environmental cleanup and has been extensively studied
since the inception of biodegradation. These studies, however, are diverse and scattered; there is an imperative need to consolidate,
summarize, and review the current status of aromatics biodegradation. The first part of this review briefly discusses the
catabolic mechanisms and describes the current status of aromatics biodegradation. Emphasis is placed on monocyclic, polycyclic,
and chlorinated aromatic hydrocarbons because they are the most prevalent aromatic contaminants in the environment. Among
monocyclic aromatic hydrocarbons, benzene, toluene, ethylbenzene, and xylene; phenylacetic acid; and structurally related
aromatic compounds are highlighted. In addition, biofilms and their applications in biodegradation of aromatic compounds are
briefly discussed. In recent years, various biomolecular approaches have been applied to design and understand microorganisms
for enhanced biodegradation. In the second part of this review, biomolecular approaches, their applications in aromatics biodegradation,
and associated biosafety issues are discussed. Particular attention is given to the applications of metabolic engineering,
protein engineering, and “omics” technologies in aromatics biodegradation. 相似文献
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Narasimharao V. Marella Brandon Seifert Priyadharsini Nagarajan Satrajit Sinha Ronald Berezney 《Journal of cellular physiology》2009,221(1):139-146
Undifferentiated human epidermal keratinocytes are self‐renewing stem cells that can be induced to undergo a program of differentiation by varying the calcium chloride concentration in the culture media. We utilize this model of cell differentiation and a 3D chromosome painting technique to document significant changes in the radial arrangement, morphology, and interchromosomal associations between the gene poor chromosome 18 and the gene rich chromosome 19 territories at discrete stages during keratinocyte differentiation. We suggest that changes observed in chromosomal territorial organization provides an architectural basis for genomic function during cell differentiation and provide further support for a chromosome territory code that contributes to gene expression at the global level. J. Cell. Physiol. J. Cell. Physiol. 221: 139–146, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Histone H2A.Z Regulates the Expression of Several Classes of Phosphate Starvation Response Genes But Not as a Transcriptional Activator 总被引:1,自引:0,他引:1