Tipología y estructura de los estados antiguos de Mesoamérica.

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La evolución del poder entre los mayas antiguos.

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Cationic 5,10,15,20-tetrakis(n-methylpyridinium-4-yl)porphyrin Fully Intercalates At 5 \u27-cg-3 \u27 Steps Of Duplex Dna In Solution

The interaction of 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)p (T4MPyP(4+)) with the oligonucleotide DNA duplex [d(GCACGTGC)](2) was studied by two-dimensional (1)H NMR spectroscopy, optical absorbance, circular dichroism, and molecular dynamics simulation employing particle mesh Ewald methods. T4MPyP(4+) is one of the largest aromatic molecules for which intercalative binding to DNA has been proposed, although this has been called into question by recent X-ray crystallographic work [Lipscomb et al. (1996) Biochemistry 35, 2818-2823]. T4MPyP(4+) binding to [d(GCACGTGC)](2) produced a single set of (mostly) upfield-shifted DNA resonances in slow exchange with the resonances of the free DNA. Intra- and intermolecular NOEs observed in the complex showed that the porphyrin intercalates at the central 5\u27-CG-3\u27 step of the DNA duplex without disrupting the flanking base pairs. Absorption and circular dichroism spectra of the complex also support intercalative binding. Molecular dynamics simulations (using explicit solvent and PME methods), carried out for fully and partially intercalated complexes, yielded stable trajectories and plausible structures, but only the symmetrical, fully intercalated model agreed with NOESY data. Stable hydrogen bonding was observed during 600 ps of MD simulation for the base pairs flanking the binding site

Photo Processes On Self-associated Cationic Porphyrins And Plastocyanin Complexes 1. Ligation Of Plastocyanin Tyrosine 83 Onto Metalloporphyrins And Electron-transfer Fluorescence Quenching

The spectroscopic properties of the self-associated complexes formed between the anionic surface docking site of spinach plastocyanin and the cationic metalloporphyrins, in which the tyrosine 83 (Y83) moiety is placed just below the docking site, tetrakis(N-methyl-4-pyridyl)porphyrin (Pd(II)TMPyP4+ and Zn(II)TMPyP4+), have been studied and reported herein. The fluorescence quenching phenomenon of the self-assembled complex of Zn(II)TMPyP4+/plastocyanin has also been discovered. The observed red-shifting of the Soret and Q-bands of the UV-visible spectra, ca. 9 nm for Pd(II)TMPyP4+/plastocyanin and ca. 6 nm for the Zn(II)TMPyP4+/ plastocyanin complexes, was explained in terms of exciton theory coupled with the Gouterman model. Thus, the hydroxyphenyl terminus of the Y83 residue of the self-associated plastocyanin/cationic porphyrin complexes was implicated in the charge-transfer ligation with the central metal atoms of these metalloporphyrins. Moreover, ground-state spectrometric-binding studies between Pd(II)TMPyP4+ and the Y83 mutant plastocyanin (Y83F-PC) system proved that Y83 moiety of plastocyanin played a critical role in the formation of such ion-pair complexes. Difference absorption spectra and the Job\u27s plots showed that the electrostatic attractions between the cationic porphyrins and the anionic patch of plastocyanin, bearing the nearby Y83 residue, led to the predominant formation of a self-associated 1:1 complex in the ground-state with significantly high binding constants (K = (8.0 +/- 1.1) x 10(5) M-1 and (2.7 +/- 0.8) x 10(6) M-1 for Pd(II)TMPyP4+ and zinc variant, respectively) in low ionic strength buffer, 1 mM KCl and 1 mM phosphate buffer (pH 7.4). Molecular modeling calculations supported the formation of a 1: 1 self-associated complex between the porphyrin and plastocyanin with an average distance of ca. 9 A between the centers of mass of the porphyrin and Y83 positioned just behind the anionic surface docking site on the protein surface. The photoexcited singlet state of Zn(II)-TMPyP4+ was quenched by the Y83 residue of the self-associated plastocyanin in a static mechanism as evidenced by steady-state and time-resolved fluorescence experiments. Even when all the porphyrin was complexed (more than 97%), significant residual fluorescence from the complex was observed such that the amplitude of quenching of the singlet state of uncomplexed species was enormously obscured

Gout: from Hippocrates till the modern time

Gout (podagra) is one of the most ancient articular diseases. Its accurate mechanisms and causes were delineated only during the last century. Major historical investigatory steps are described in relation to causality and pathogenesis of the disease from Hippocrates ages till the modern time. The newest genetic and epidemiologic aspects of the disease are presented in this article

Exocyclic Carbons Adjacent to the N6 of Adenine are Targets for Oxidation by the Escherichia coli Adaptive Response Protein AlkB

The DNA and RNA repair protein AlkB removes alkyl groups from nucleic acids by a unique iron- and α-ketoglutarate-dependent oxidation strategy. When alkylated adenines are used as AlkB targets, earlier work suggests that the initial target of oxidation can be the alkyl carbon adjacent to N1. Such may be the case with ethano-adenine (EA), a DNA adduct formed by an important anticancer drug, BCNU, whereby an initial oxidation would occur at the carbon adjacent to N1. In a previous study, several intermediates were observed suggesting a pathway involving adduct restructuring to a form that would not hinder replication, which would match biological data showing that AlkB almost completely reverses EA toxicity in vivo. The present study uses more sensitive spectroscopic methodology to reveal the complete conversion of EA to adenine; the nature of observed additional putative intermediates indicates that AlkB conducts a second oxidation event in order to release the two-carbon unit completely. The second oxidation event occurs at the exocyclic carbon adjacent to the N[superscript 6] atom of adenine. The observation of oxidation of a carbon at N[superscript 6] in EA prompted us to evaluate N[superscript 6]-methyladenine (m6A), an important epigenetic signal for DNA replication and many other cellular processes, as an AlkB substrate in DNA. Here we show that m6A is indeed a substrate for AlkB and that it is converted to adenine via its 6-hydroxymethyl derivative. The observation that AlkB can demethylate m6A in vitro suggests a role for AlkB in regulation of important cellular functions in vivo.National Institutes of Health (U.S.) (Grant number CA080024)National Institutes of Health (U.S.) (Grant number CA26731)National Institutes of Health (U.S.) (Grant number ES02109

Differential modes of DNA binding by mismatch uracil DNA glycosylase from Escherichia coli: implications for abasic lesion processing and enzyme communication in the base excision repair pathway

Mismatch uracil DNA glycosylase (Mug) from Escherichia coli is an initiating enzyme in the base-excision repair pathway. As with other DNA glycosylases, the abasic product is potentially more harmful than the initial lesion. Since Mug is known to bind its product tightly, inhibiting enzyme turnover, understanding how Mug binds DNA is of significance when considering how Mug interacts with downstream enzymes in the base-excision repair pathway. We have demonstrated differential binding modes of Mug between its substrate and abasic DNA product using both band shift and fluorescence anisotropy assays. Mug binds its product cooperatively, and a stoichiometric analysis of DNA binding, catalytic activity and salt-dependence indicates that dimer formation is of functional significance in both catalytic activity and product binding. This is the first report of cooperativity in the uracil DNA glycosylase superfamily of enzymes, and forms the basis of product inhibition in Mug. It therefore provides a new perspective on abasic site protection and the findings are discussed in the context of downstream lesion processing and enzyme communication in the base excision repair pathway

Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG)

The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N[superscript 6]-ethenoadenine (εA). The crystal structures of AAG bound to εA have provided insights into the structural basis for substrate recognition, base excision, and exclusion of normal purines and pyrimidines from its substrate recognition pocket. In this study, we explore the substrate specificity of full-length and truncated Δ80AAG on a library of oligonucleotides containing structurally diverse base modifications. Substrate binding and base excision kinetics of AAG with 13 damaged oligonucleotides were examined. We found that AAG bound to a wide variety of purine and pyrimidine lesions but excised only a few of them. Single-turnover excision kinetics showed that in addition to the well-known εA and Hx substrates, 1-methylguanine (m1G) was also excised efficiently by AAG. Thus, along with εA and ethanoadenine (EA), m1G is another substrate that is shared between AAG and the direct repair protein AlkB. In addition, we found that both the full-length and truncated AAG excised 1,N[superscript 2]-ethenoguanine (1,N[superscript 2]-εG), albeit weakly, from duplex DNA. Uracil was excised from both single- and double-stranded DNA, but only by full-length AAG, indicating that the N-terminus of AAG may influence glycosylase activity for some substrates. Although AAG has been primarily shown to act on double-stranded DNA, AAG excised both εA and Hx from single-stranded DNA, suggesting the possible significance of repair of these frequent lesions in single-stranded DNA transiently generated during replication and transcription.United States. National Institutes of Health (grant ES05355)United States. National Institutes of Health (grant CA75576)United States. National Institutes of Health (grant CA55042)United States. National Institutes of Health (grant ES02109)United States. National Institutes of Health (grant T32-ES007020)United States. National Institutes of Health (grant CA80024)United States. National Institutes of Health (grant CA26731