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1.
《Journal of molecular biology》2021,433(15):167097
DNA glycosylases remove damaged or modified nucleobases by cleaving the N-glycosyl bond and the correct nucleotide is restored through subsequent base excision repair. In addition to excising threatening lesions, DNA glycosylases contribute to epigenetic regulation by mediating DNA demethylation and perform other important functions. However, the catalytic mechanism remains poorly defined for many glycosylases, including MBD4 (methyl-CpG binding domain IV), a member of the helix-hairpin-helix (HhH) superfamily. MBD4 excises thymine from G·T mispairs, suppressing mutations caused by deamination of 5-methylcytosine, and it removes uracil and modified uracils (e.g., 5-hydroxymethyluracil) mispaired with guanine. To investigate the mechanism of MBD4 we solved high-resolution structures of enzyme-DNA complexes at three stages of catalysis. Using a non-cleavable substrate analog, 2′-deoxy-pseudouridine, we determined the first structure of an enzyme-substrate complex for wild-type MBD4, which confirms interactions that mediate lesion recognition and suggests that a catalytic Asp, highly conserved in HhH enzymes, binds the putative nucleophilic water molecule and stabilizes the transition state. Observation that mutating the Asp (to Gly) reduces activity by 2700-fold indicates an important role in catalysis, but probably not one as the nucleophile in a double-displacement reaction, as previously suggested. Consistent with direct-displacement hydrolysis, a structure of the enzyme-product complex indicates a reaction leading to inversion of configuration. A structure with DNA containing 1-azadeoxyribose models a potential oxacarbenium-ion intermediate and suggests the Asp could facilitate migration of the electrophile towards the nucleophilic water. Finally, the structures provide detailed snapshots of the HhH motif, informing how these ubiquitous metal-binding elements mediate DNA binding. 相似文献
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Binding of the cationic tetra(tributylammoniomethyl)-substituted hydroxoaluminum phthalocyanine (AlPcN4) to bilayer lipid membranes was studied by fluorescence correlation spectroscopy (FCS) and intramembrane field compensation (IFC) methods. With neutral phosphatidylcholine membranes, AlPcN4 appeared to bind more effectively than the negatively charged tetrasulfonated aluminum phthalocyanine (AlPcS4), which was attributed to the enhancement of the coordination interaction of aluminum with the phosphate moiety of phosphatidylcholine by the electric field created by positively charged groups of AlPcN4. The inhibitory effect of fluoride ions on the membrane binding of both AlPcN4 and AlPcS4 supported the essential role of aluminum-phosphate coordination in the interaction of these phthalocyanines with phospholipids. The presence of negative or positive charges on the surface of lipid membranes modulated the binding of AlPcN4 and AlPcS4 in accord with the character (attraction or repulsion) of the electrostatic interaction, thus showing the significant contribution of the latter to the phthalocyanine adsorption on lipid bilayers. The data on the photodynamic activity of AlPcN4 and AlPcS4 as measured by sensitized photoinactivation of gramicidin channels in bilayer lipid membranes correlated well with the binding data obtained by FCS and IFC techniques. The reduced photodynamic activity of AlPcN4 with neutral membranes violating this correlation was attributed to the concentration quenching of singlet excited states as proved by the data on the AlPcN4 fluorescence quenching. 相似文献
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THE TIMING OF DIVISION IN CHLAMYDOMONAS 总被引:3,自引:2,他引:1
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The fully enclosed Taiaro lagoon is hypersaline (42.5 psu) and non-tidal; constant salinity and water level result from strong
evaporation balanced by low percolation through the lagoon floor. Seawater can flow over the atoll rim during exceptionally
high seas and may then replenish lagoonal communities with propagules of oceanic origin. The distinctive water chemistry of
the lagoon suggests a possible way of identifying these immigrants. We established this potential by analysing stable isotopes
of carbon and oxygen in the recent growth layers of otoliths of two adult reef fishes, Chaetodon ulietensis and Acanthurus triostegus, collected from both sides of the atoll rim. Fish from the two locations were discriminated by their isotopic signatures,
suggesting that analysis of the microchemical signatures deposited during the larval development could be used in future work
to determine which individuals and species complete their life-cycles in this unusual lagoon.
Accepted: 28 August 1997 相似文献
8.
The mechanism of the binding of 2-(4'-hydroxyphenylazo)benzoic acid (HABA) to bovine serum albumin was studied by relaxation methods as well as the binding isotherm using gel chromatography. A single relaxation was observed over a wide range of HABA concentration except at the extremes of high concentration where another slow process was observed. The concentration dependence of the reciprocal relaxation time of the fast process decreased monotonically with increase in concentration of HABA at constant polymer concentration. The data were analyzed on the basis of Brown's domain structure model and were found to be consistent with a sequential binding mechanism. The azohydrazon tautomerism of HABA was identified with the intramolecular step of the complex. The activation parameters of the step, determined from the temperature dependence of the relaxation time of the fast process, showed that this step is rate limited by an enthalpy barrier in both forward and backward directions. Comparison of the activation parameters with those of other serum albumin-ligand systems suggests that there is an enthalpy-entropy compensation in the activation process of the intramolecular step with the compensation temperature at about 270 K; the enthalpy-entropy compensation is thought to be related to the hydrophobic nature of the ligand. 相似文献
9.
F. CROUTE D. DUPOUY J. P. CHARLEY J. P. SOLEILHAVOUP H. PLANEL 《The Journal of eukaryotic microbiology》1980,27(1):132-135
SYNOPSIS Catalase activity of Paramecium tetraurelia decreased during autogamy and recovered to normal 5 days later. Autogamy also caused changes in the ciliate's sensitivity to natural ionizing radiations—the decrease in cell growth rate previously described in shielded cultures did not occur when autogamous cells were used. Maximum effect of shielding was observed in 11-day-old postautogamous cells. the role of the catalase in the mechanism of natural irradiation effect is discussed. 相似文献
10.
Rupam Sarma 《Inorganica chimica acta》2009,362(6):1681-55
The coordination polymerization from lead(II) nitrate on reaction with 4-nitrobenzoic acid and pyridine N-oxide at room temperature passes through stepwise ligand substitution reaction. An intermediate polymer [Pb(NB)(PyO)2(NO3)]n (where NB = 4-nitrobenzoate, PyO = Pyridine N-oxide) is formed to give the final polymer [Pb(NB)2(PyO)]n. A hydrated mononuclear complex [Pb(NB)2(PyO)(H2O)] is also formed if rigorous anhydrous condition is not maintained. The reaction is extended to 4,4′-bipyridyl N-oxide (BPNO), which initially gives a coordination polymer [Pb2(NO3)(NB)3(BPNO)2]n which gets converted to another coordination polymer [Pb(NB)2(BPNO)2]n. All these complexes are structurally characterized. 相似文献