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991.
Internal water molecules and H-bonding in biological macromolecules: a review of structural features with functional implications. 总被引:3,自引:5,他引:3 下载免费PDF全文
E. Meyer 《Protein science : a publication of the Protein Society》1992,1(12):1543-1562
Conserved structural patterns of internal water molecules and/or H-bond chains were observed and are here correlated in this review, which then describes two functional properties: equilibration of hydrostatic pressure and proton transport. Available evidence in support of these hypotheses is presented, together with suggested experiments to test them. High-resolution crystal structures of a variety of proteins were studied with interactive computer graphics. Conserved H-bonding linkages may be used as a paradigm for a rationalization of proton transport in membranes. The concept of the "proton wire," which links buried active-site amino acids with the surface of the protein raises the more general question of the functional role of the various molecular components. 相似文献
992.
The DNA-binding protein from stationary phase (Dps) protein family plays an important role in protecting microorganisms from oxidative and nutritional stresses. In silico analysis of the promoter region of alr3808, a dpsA homologue from the cyanobacterium Nostoc sp. PCC7120 shows putative iron-boxes with high homology with those recognized by FurA (ferric uptake regulator). Evidence for the modulation of dpsA by FurA was obtained using in vitro and in vivo approaches. SELEX linked to PCR was used to identify PdpsA as a FurA target. Concurrently, EMSA assays showed high affinity of FurA for the dpsA promoter region. DpsA expression analysis in an insertional mutant of the alr1690-αfurA message (that exhibited an increased expression of FurA) showed a reduced synthesis of DpsA. These studies suggest that FurA plays a significant role in the regulation of the DpsA. 相似文献
993.
The structural chemistry of dihalogenopalladium(II) and platinum(II) complexes of 2-organochalcogenomethylpyridine ligands is described. Complexes with a methyl group in the 6-position of the pyridyl ring, 6-MepyCH2ER, form dimeric complexes [trans-PdX2(μ-6-MepyCH2SePh-N,Se)]2 (X = Br (1), I (2)) or mononuclear complexes trans-PdI2(6-MepyCH2SR-N)2 (R = Me (5), Ph (6)). Absence of a 6-methyl substituent results in the bidentate configuration observed for PdI2(pyCH2SePh-N,Se) (3) and PdI2(4-MepyCH2SMe-N,S) (4). Related platinum(II) complexes are mononuclear including PtCl2(6-MepyCH2SPh-N,S) (8) as an analogue of trimeric [trans-PdCl2(μ-6-MepyCH2SPh-N,S)]3. Differences between palladium and platinum appear to result from a combination of steric and electronic factors. 相似文献
994.
The preparation and characterization of organolithium O,C,O-pincer compound [2,6-(tBuOCH2)2C6H3]-Li (1) is described. The X-ray diffraction techniques revealed the dimeric structure of 1 consisting of two lithium atoms Li(1) and Li(2) and two monoanionic chelating aryl ligands in the solid state, where each lithium atom is coordinated by two oxygen atoms of two different ligands. The NMR spectroscopy and cryoscopy measurements established monomer-dimer equilibrium of 1 in concentrated solutions of non-coordinated solvents, while the diluted solutions of 1 consist of monomer only. 相似文献
995.
Maaser K Sutter AP Krahn A Höpfner M Grabowski P Scherübl H 《Biochemical and biophysical research communications》2004,324(2):878-886
Specific ligands of the peripheral benzodiazepine receptor (PBR) have been shown to induce both apoptosis and G1/G0 cell cycle arrest in colorectal cancers. The signaling pathways leading to cell cycle arrest are still unknown. Using cDNA array technology, we identified signaling molecules involved in cell cycle arrest induced by the PBR ligands FGIN-1-27 and PK 11195. Differential gene expression was confirmed by semi-quantitative RT-PCR or Western blot analysis of gene products. The PBR ligand-mediated signaling involved the upregulation of the cyclin-dependent kinase inhibitors p21WAF1/CIP1 and p27Kip1, cdc16, and the cell cycle inhibitors gadd45 and gadd153, the downregulation of the cyclins D1 and B1, as well as the inactivation of ERK1/2. The p21-deficient colorectal cancer cell line HCT116 p21-/- was significantly less sensitive to PBR ligands than the parental HCT116 wild-type cells, demonstrating the functional involvement of p21WAF1/CIP1 in PBR ligand-mediated G1 arrest. This study thus revealed PBR ligand-triggered signaling pathways leading to cell cycle arrest. Moreover, we showed the functional implication and interaction of differentially expressed gene products and provided a model of signaling pathways involved in PBR ligand-induced G1 arrest. These results form the basis for future PBR ligand-mediated therapeutic approaches. 相似文献
996.
灭活铜绿假单胞菌适体的筛选 总被引:1,自引:0,他引:1
利用指数富集配基的系统进化(SELEX)技术,以灭活的铜绿假单胞菌为靶标,从体外合成的96 nt随机ssDNA文库中筛选与铜绿假单胞菌特异结合的适体.在第12轮和第14轮与其它假单胞菌属进行反筛策略,并进行了适体的结合亲和力的测定,再分别利用ClustalX、Mega2和Mfold sever软件分析适体的一级和二级结构.研究结果表明,经过15轮筛选,随机ssDNA文库与铜绿假单胞菌结合的A值从0.022上升到0.448.反筛与未反筛的结合A比值最高比为53倍.经过第15轮反筛后的24个阳性克隆子测序,根据软件分析,其可分成10个家族.每个家族都有其共同的保守序列(除第10个家族),其中有2条序列几乎完全一致(F23和F47),同源性达到97%,A值分别高达1.598和1.508,Kd为14.55和77.46 nmol/L,间接说明适体与铜绿假单胞菌的结合力明显增高. 相似文献
997.
1,4,7,10-Tetrakis{[N-(1H-imidazol-2-yl)carbamoyl]methyl}-1,4,7,10-tetraazacyclododecane (dotami), a tetra(1H-imidazol-2-yl) derivative of the well-studied octadentate 1,4,7,10-tetrakis[(carbamoyl)methyl]-1,4,7,10-tetraazacyclododecane (dotam) ligand, was synthesized by reaction of 1,4,7,10-tetraazacyclododecane with N-(1H-imidazol-2-yl)chloroacetamide in high yield. Its tricationic thulium complex was isolated as a water-soluble chloride salt. The detection of the mildly acidic amide and amine protons by direct proton NMR in aqueous solution was unsuccessful, but such exchangeable protons could be detected via their chemical exchange-dependent saturation transfer (CEST) effect. The observed CEST effect was distinctly different from that found for respective dotam complexes and is, therefore, ascribed to exchangeable protons associated with the imidazole substituent. 相似文献
998.
Molecular dynamics (MD) simulations have been undertaken in order to investigate the collective solvent reorganization following
an instantaneous electronic charge transfer between distinct atomic sites of diatomic probe molecules immersed in methanol–water
mixtures. Our previous studies of solvation dynamics in these mixtures [28,29] are extended here to the analysis of nonequilibrium
time-dependent solute–solvent site–site pair distribution functions for the equimolar mixture using two different solute sizes.
This has allowed us to obtain a more detailed picture of the solvent reorganization in response to the solute's excitation.
Special attention is devoted to the dynamics of rupture and formation of hydrogen bonds between the smaller probe solute and
solvent molecules, and its relationship to the molecular mechanisms of solvation dynamics in these systems on distinct time
scales.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
999.
Joong-Youn Shim Alexander C. Bertalovitz Debra A. Kendall 《The Journal of biological chemistry》2012,287(46):38741-38754
SR141716A binds selectively to the brain cannabinoid (CB1) receptor and exhibits a potent inverse agonist/antagonist activity. Although SR141716A, also known as rimonabant, has been withdrawn from the market due to severe side effects, there remains interest in some of its many potential medical applications. Consequently, it is imperative to understand the mechanism by which SR141716A exerts its inverse agonist activity. As a result of using an approach combining mutagenesis and molecular dynamics simulations, we determined the binding mode of SR141716A. We found from the simulation of the CB1-SR141716A complex that SR141716A projects toward TM5 to interact tightly with the major binding pocket, replacing the coordinated water molecules, and secures the Trp-3566.48 rotameric switch in the inactive state to promote the formation of an extensive water-mediated H-bonding network to the highly conserved SLAXAD and NPXXY motifs in TM2/TM7. We identify for the first time the involvement of the minor binding pocket formed by TM2/TM3/TM7 for SR141716A binding, which complements the major binding pocket formed by TM3/TM5/TM6. Simulation of the F1742.61A mutant CB1-SR141716A complex demonstrates the perturbation of TM2 that attenuates SR141716A binding indirectly. These results suggest SR141716A exerts inverse agonist activity through the stabilization of both TM2 and TM5, securing the Trp-3566.48 rotameric switch and restraining it from activation. 相似文献
1000.
C. Pérez Olmo 《Inorganica chimica acta》2007,360(5):1510-1516
The Zn-OH2 and Zn-OH complexes of the new tris(pyrazolyl)borate ligands with pyridyl and carboxamido substituents were investigated for their reactivity towards hydrolyzeable substrates. Tp4−Py,MeZn-OH inserted CO2 and CS2 in methanol forming the Zn-OCOOMe and Zn-SCSOMe products. In non-aqueous media, both types of complexes with both types of substituents on the Tp ligands effected stoichiometric cleavage of tris(p-nitrophenyl)phosphate and p-nitrophenyl acetate. In solutions containing water and the MOPS buffer, up to eight p-nitrophenyl groups per equivalent of zinc complex could be cleaved from the esters, and the resulting bis(p-nitrophenyl)phosphate was also degraded to mono(p-nitrophenyl)phosphate. This is the first time that pyrazolylborate-zinc complexes have shown catalytic activity in hydrolytic reactions. 相似文献