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61.
Tolerance to Diazepam-Induced Motor Impairment: A Study with GABAA Receptor α6 Subunit Knockout Mice
Development of tolerance to motor-impairing effects of repeated administration of moderate diazepam doses (5.0–7.5 mg/kg; three times daily PO 3 weeks) was compared between mice deficient in the cerebellar granule cell–restricted GABAA receptor 6 subunit and their wild-type controls. The 6–/– mice were more impaired by the initial challenge doses of diazepam (5 or 10 mg/kg) than their controls, but acquired partial tolerance by the second tests with the same doses 4–7 days later. Chronic treatment produced complete tolerance in both mouse lines. Ligand autoradiography revealed a significant reduction in baseline benzodiazepine and chloride channel site-bindings in various regions of the 6–/– brains, but the chronic diazepam treatment did not consistently alter baseline or benzodiazepine site agonist and inverse agonist-modulated binding in the 6–/– and wildtype mice. The results indicate that tolerance to motor-impairing actions of diazepam is independent of the diazepam-insensitive 6 subunit-containing receptors, which rules out the possibility that tolerance emerges as an increase in structurally benzodiazepine-insensitive receptor population. 相似文献
62.
Mechanism of bactericidal and fungicidal activities of textiles covalently modified with alkylated polyethylenimine 总被引:10,自引:0,他引:10
Our previous studies have led to a novel "nonrelease" approach to making materials bactericidal by covalently attaching certain moderately hydrophobic polycations to their surfaces. In the present work, this strategy is extended beyond the heretofore-used nonporous materials to include common woven textiles (cotton, wool, nylon, and polyester). Pieces of such cloths derivatized with N-hexylated+methylated high-molecular-weight polyethylenimine (PEI) are strongly bactericidal against several airborne Gram-positive and Gram-negative bacteria. In contrast, the immobilized and N-alkylated PEIs of low molecular weight have only a weak, if any, bactericidal activity. These findings support a mechanism of the antibacterial action whereby high-molecular-weight and hydrophobic polycationic chains penetrate bacterial cell membranes/walls and fatally damage them. The bactericidal textiles prepared herein are lethal not only to pathogenic bacteria but to fungi as well. 相似文献
63.
Medium-chain-length fatty acids, such as nonanoic (9:0) and octanoic (8:0) acids, are more toxic to Ralstonia eutropha than volatile fatty acids such as acetic, propionic and butyric acids. Nonanoic acid was degraded to acetic and propionic acids via -oxidation by Ralstonia eutropha for cell growth and synthesis of polyhydroxyalkanoates (PHAs). In a mixture of the fatty acids, utilization of nonanoic acid was depressed by acetic and propionic acids, and vice versa. The PHA accumulation from the volatile fatty acids was decreased from 53% (w/w) of dry cell mass to 23% due to the nonanoic acid. Similar phenomena were also observed with octanoic acid and its metabolic intermediates, acetic and butyric acids. 相似文献
64.
Pang YP 《Proteins》2001,45(3):183-189
I report herein two 2.0 ns (1.0 fs time step) MD simulations of two zinc complexes bridged by a hydroxide in phosphotriesterase (PTE) employing the nonbonded method and the cationic dummy atom method that uses virtual atoms to impose orientational requirement for zinc ligands. The cationic dummy atom method was able to simulate the four-ligand coordination of the two zinc complexes in PTE. The distance (3.39 +/- 0.07A) between two nearby zinc ions in the time-average structure of PTE derived from the MD simulation using the cationic dummy atoms matched that in the X-ray structure (3.31 +/- 0.001A). Unequivocally, the time-average structure of PTE was able to fit into the experimentally determined difference electron density map of the corresponding X-ray structure. The results demonstrate the practicality of the cationic dummy atom method for MD simulations of zinc proteins bound with multiple zinc ions. In contrast, a 2.0 ns (1.0 fs time step) MD simulation using the nonbonded method revealed a striking difference in the active site between the X-ray structure and the time-average structure that was unable to fit into the density map of PTE. The results suggest that caution should be used in the MD simulations using the nonbonded method. 相似文献
65.
Allan J. Canty Jim PatelMichel Pfeffer Brian W. SkeltonAllan H. White 《Inorganica chimica acta》2002,327(1):20-25
Neutral palladium(IV) complexes containing the bis(pyrazol-1-yl)borate ligand, PdMe3{(pz)2BH2}(L) [L=py-d5 (4), PMe2Ph (6)], are generated in solution by oxidative addition of iodomethane to [PdMe2{(pz)2BH2}]− at −70 °C followed by addition of L; the Pd(IV) complexes reductively eliminate ethane above 0 °C. Stable Pt(IV) analogues of 4 and 6 have been isolated, and comparison of NMR spectra for Pd(IV) and Pt(IV) species support structural assignments for the unstable Pd(IV) complexes. The complex PtMe3{(pz)2BH2}(py) (1a) has been characterised by X-ray diffraction, together with Pt(mq)Me2{(pz)2BH2} (2) (mq=8-methylquinolinyl); both complexes show a fac-PtC3 configuration for Pt(IV), and for 2 the PtN distances are ∼0.03 Å shorter than in the isostructural Pd(IV) complex. 相似文献
66.
Reported crystallographic data and calculated molecular models indicated that chlorophyll (Chl) a and bacteriochlorophyll (BChl) a tend to bind the fifth ligand on the side of the macrocycle where the C132-(R)-methoxycarbonyl moiety protrudes (denoting the ‘back’ side). The crystal structures of 34 photosynthetic proteins possessing
(B)Chl cofactors revealed that most of Chl a and BChl a (and b) are coordinated by any peptidyl residue (e.g., histydyl-imidazolyl group), peptidyl backbone or water from the ‘back’ side.
Almost all the cofactors that bind a water molecule as the fifth ligand in these proteins have a ‘back’ configuration. Theoretical
model calculations for methyl chlorophyllide a (MeChlid a) and methyl bacteriochlorophyllide a (MeBChlid a) bound to an imidazole molecule indicated that the ‘back’ side is energetically favored for the ligand binding. These results
are consistent with the fact that ethyl chlorophyllide a (EtChlid a) dihydrate crystal consists of the ‘back’ complex. The modeling also showed that both removal and stereochemical inverse
of the C132-methoxycarbonyl group affect the relative stability between the ‘back’ and ‘face’ complexes. The effect of the C132-moiety on the choice of the macrocycle side for the ligand binding is discussed in relation to the function of P700.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
67.
Rhizopus nigricans was cultivated in a liquid medium using lemon, mandarin, orange, pear and melon peel or artichoke bracts as the carbon source. In all cultures, a carbohydrate polymer fraction remained resistant to fermentation. These fractions were isolated in gram amounts and characterised. The molecular weight distribution of the fractions and its sugar composition resembles those of the hairy-regions of the pectins. In the fractions, four main carbohydrates were found: 4-7 mol% Rha, 42-59 mol% Ara, 7-14 mol% Gal, 17-33 mol% GalA. 相似文献
68.
Interconversion reactions of cyclodextrin glycosyltransferase (CGTase) among cyclodextrin (CD) homologues were experimentally investigated using each CD as a substrate in an aqueous, two-phase-forming polymer solution of dextran and polyethylene glycol. Degradation rate of -CD was highest and that of -CD was lowest among -, - and -CD with Bacillus macerans CGTase. Degradation of each CD was accelerated with dextran, while decelerated with polyethylene glycol. 相似文献
69.
The bis(oxazoline) ligand, 2,2-bis[4(R)-phenyl-1,3-oxazolon-2-yl]propane (bpop), was introduced to the η6-benzenemthenium(II) moiety on treatment with [Ru(η6-C6H6)Cl2]2 to give [Ru(η6-C6H6)(bpop)Cl]+. Aquo and amine complexes [Ru(η6-C6H6)(bpop)(L)]2+ (L = H2O (1), NH2R; R = H (2) , Me (3) , and n-Bu (4) ) were prepared by treating the chloride complex with AgBF4 in the presence of L. X-ray structure determinations of 1 and 3 were carried out. Both complexes possessed a three-leg piano stool structure with the N or O donors located at the three comers of a pseudo octahedron. The aquo complex 1 exhibited a dynamic NMR feature in which two magnetically nonequivalent oxazoline parts observed at lower temperatures were interchanged with each other at higher temperatures. This observation was ascribed to the formation of a C2-symmetric 16-electron intermediate via Ru-OH2 cleavage, which is slower in acetone than in dichloromethane owing to more effective solvation by acetone around hydrogens of the coordinated water molecule. The two diastereotopic N-hydrogens of 4 underwent deuterium exchange with CD3OD with greatly different rates from each other owing to different energy of NHO (D) (CD3) interaction. Carboxylate and sulfonate ions (A−) formed second sphere complexes with 4 by means of NHA− hydrogen bonding, as evidenced by continuous shift of NH2 resonances with increasing amounts of the anions added. 相似文献
70.
Alberts IL Nadassy K Wodak SJ 《Protein science : a publication of the Protein Society》1998,7(8):1700-1716
The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations. 相似文献