Método para a predição do desfecho do tratamento de doenças humanas utilizando fármacos metabolizados pela N-acetiltransferase 2 humana (NAT2) com base em polimorfismos genéticos

Em 04/01/2016: Anuidade de pedido de patente de invenção no prazo ordinário.DepositadaMétodo para a predição do desfecho do tratamento de doenças humanas utilizando fármacos metabolizados pela N- acetiltransferase 2 humana (NAT2) com base em polimorfismos genéticos. A presente invenção está relacionada ao campo da Biologia Molecular e Genâmica, especialmente a Farmacogenâmica. A invenção descreve a presença de novos polimorfismos no gene que codifica para a enzima Arilamina N-acetiltransferase 2 humana (NAT2), a qual é responsável pela metabolização de fármacos importantes na terapêutica de várias doenças de etiologias diversas, bem como de inúmeras toxinas e carcinógenos presentes em alimentos, cigarro e no ambiente. A presente invenção inclui metodologia passível de utilização na terapêutica utilizando os polimorfismos descritos

The Purine Bias of Coding Sequences is Determined by Physicochemical Constraints on Proteins

For this report, we analyzed protein secondary structures in relation to the statistics of three nucleotide codon positions. The purpose of this investigation was to find which properties of the ribosome, tRNA or protein level, could explain the purine bias (Rrr) as it is observed in coding DNA. We found that the Rrr pattern is the consequence of a regularity (the codon structure) resulting from physicochemical constraints on proteins and thermodynamic constraints on ribosomal machinery. The physicochemical constraints on proteins mainly come from the hydropathy and molecular weight (MW) of secondary structures as well as the energy cost of amino acid synthesis. These constraints appear through a network of statistical correlations, such as (i) the cost of amino acid synthesis, which is in favor of a higher level of guanine in the first codon position, (ii) the constructive contribution of hydropathy alternation in proteins, (iii) the spatial organization of secondary structure in proteins according to solvent accessibility, (iv) the spatial organization of secondary structure according to amino acid hydropathy, (v) the statistical correlation of MW with protein secondary structures and their overall hydropathy, (vi) the statistical correlation of thymine in the second codon position with hydropathy and the energy cost of amino acid synthesis, and (vii) the statistical correlation of adenine in the second codon position with amino acid complexity and the MW of secondary protein structures. Amino acid physicochemical properties and functional constraints on proteins constitute a code that is translated into a purine bias within the coding DNA via tRNAs. In that sense, the Rrr pattern within coding DNA is the effect of information transfer on nucleotide composition from protein to DNA by selection according to the codon positions. Thus, coding DNA structure and ribosomal machinery co-evolved to minimize the energy cost of protein coding given the functional constraints on proteins

Mining of potential drug targets through the identification of essential and analogous enzymes in the genomes of pathogens of <i>Glycine max</i>, <i>Zea mays</i> and <i>Solanum lycopersicum</i>

<div><p>Pesticides are one of the most widely used pest and disease control measures in plant crops and their indiscriminate use poses a direct risk to the health of populations and environment around the world. As a result, there is a great need for the development of new, less toxic molecules to be employed against plant pathogens. In this work, we employed an <i>in silico</i> approach to study the genes coding for enzymes of the genomes of three commercially important plants, soybean (<i>Glycine max</i>), tomato (<i>Solanum lycopersicum</i>) and corn (<i>Zea mays</i>), as well as 15 plant pathogens (4 bacteria and 11 fungi), focusing on revealing a set of essential and non-homologous isofunctional enzymes (NISEs) that could be prioritized as drug targets. By combining sequence and structural data, we obtained an initial set of 568 cases of analogy, of which 97 were validated and further refined, revealing a subset of 29 essential enzymatic activities with a total of 119 different structural forms, most belonging to central metabolic routes, including the carbohydrate metabolism, the metabolism of amino acids, among others. Further, another subset of 26 enzymatic activities possess a tertiary structure specific for the pathogen, not present in plants, men and <i>Apis mellifera</i>, which may be of importance for the development of specific enzymatic inhibitors against plant diseases that are less harmful to humans and the environment.</p></div

Genome Comparison of an Ancestral Isolate and a Modern Isolate of Mycobacterium tuberculosis of the Beijing Lineage from São Paulo, Brazil

Submitted by sandra infurna ([email protected]) on 2016-03-31T11:53:07Z No. of bitstreams: 1 sidra_vasconcellos_etal_IOC_2015.pdf: 154933 bytes, checksum: 4c0416a8ad804bc5b55bf7e401d4f3fc (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-03-31T12:08:13Z (GMT) No. of bitstreams: 1 sidra_vasconcellos_etal_IOC_2015.pdf: 154933 bytes, checksum: 4c0416a8ad804bc5b55bf7e401d4f3fc (MD5)Made available in DSpace on 2016-03-31T12:08:13Z (GMT). No. of bitstreams: 1 sidra_vasconcellos_etal_IOC_2015.pdf: 154933 bytes, checksum: 4c0416a8ad804bc5b55bf7e401d4f3fc (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada à Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Molecular de Microrganismos. Rio de Janeiro, RJ, Brasil.Universidade Estadual do Norte Fluminense. Laboratório de Biologia do Reconhecimento. Campos de Goytacazes, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada à Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada à Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Computacional e de Sistemas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada à Micobactérias. Rio de Janeiro, RJ, Brasil.Mycobacterium tuberculosis of the Bejing subtype (MtbB) is transmitted efficiently in high burden countries for this genotype. A higher virulence was associated with isolates of the “modern” Beijing genotype sub-lineages when compared to “ancient” ones. Here, we report the full genomes of the strain representing these two genotypes from Brazil, a country with a low incidence of MtbB

Number of potential, validated, specific and essential NISEs.

<p>Numbers in parenthesis indicate the number of enzymatic activities identified.</p

Phytopathogen specific enzymatic structural forms.

<p>Phytopathogen specific enzymatic structural forms.</p

Functional classification of the validated NISEs.

<p>Numbers in parenthesis indicate the amount of essential enzymatic activities.</p

Identification of essential, non-homologous isofunctional enzymes.

<p>Identification of essential, non-homologous isofunctional enzymes.</p