Influence of the enzyme phosphorylation state and the substrate on PKA enzyme dynamics.

cAMP-dependent protein kinase (PKA) is one of the simplest and best understood members of the protein kinase family. In a previous study, we have theoretically studied the complex between PKA and the heptapeptide substrate Kemptide by classical molecular dynamics. On the basis of the results obtained for Kemptide, the aim of the present work is to explore how the different conditions, such as phosphorylation state, substrate, and mutations of key residues affect the enzyme dynamics. We have built different models of the complex; particularly we have focused our attention on two crystallographic structures which main difference consists in their phosphorylation state. The first one has the residue Thr197 modified into a phospho-threonine (pThr197); the second one, in addition to the same Thr197, has also the residue Ser338 modified into a phospho-serine (pSer338). In addition, we have analyzed the effect of the choice of the substrate by building a model of the PKA-SP20 Michaelis complex. Finally, we have theoretically studied the effect of the mutation of the highly conserved residue Asp166 that, experimentally, leads to a decrease of the reaction rate. The results of this study give insight into the dynamical states of the enzyme and their relationship with different elements of the model, which correspond to different natural or human guided situations of the active biological system.

A QM/MM study of the phosphoryl transfer to the Kemptide substrate catalyzed by protein kinase A. The effect of the phosphorylation state of the protein on the mechanism.

We present here a theoretical study of the phosphoryl transfer catalytic mechanism of protein kinase A, which is the best known member of the large protein kinase family. We have built different theoretical models of the complete PKA-Mg(2)-ATP-substrate system to explore the two most accepted reaction pathways, using for the first time in a reaction mechanism theoretical study, the heptapeptide substrate Kemptide, which is relevant for its high efficiency and small size. The effect of the protein configuration, as modeled by two different X-ray structures with different phosphorylation states and degrees of flexibility, has been analyzed. The results indicate that the environmental conditions can influence the availability of the pathways and thus the choice of the mechanism to be followed. In addition, the roles of the two active site conserved residues, Asp166 and Lys168, have been analyzed for each reaction mechanism.

Produção e acesso a fontes de informação para a psicologia em Portugal

Este trabalho faz uma panorâmica da produção e do acesso à informação científica em publicações periódicas no campo da psicologia, em Portugal. Do ponto de vista da produção, é feito um inventário das publicações periódicaseditadas em Portugal em formato electrónico e sua distribuição ou alojamento em portais ou websites. Do ponto de vista do acesso, que bases de dados, que publicações periódicas estão disponíveis, para quem e como podem ser acedidas. Faz-se um destaque para o projecto B-On (Biblioteca do Conhecimento Online). Analisa-se a acessibilidade dos periódicos com maior impacto para a psicologia em geral e são fornecidos alguns dados para a área mais específica da psicologia da saúde, com base em pesquisas efectuadas nas bases de dados Web of Science, PubMed e Scopus.

This paper presents a panoramic view of the production and access to scientific information in periodical publications in the field of psychology in Portugal. From the point of view of production, an inventory of the periodical publications published in Portugal in electronic format, its distribution or hosting in portals or websites is made. From the point of view of access it is indicated the databases and the periodical publications available, who can have access to them and how to do it. It is highlighted the B-On project (Biblioteca do Conhecimento Online, that is, Online Knowledge Library). It is also analyzed the accessibility to the periodicals with greatest impact for general psychology and are provided some data for the More specific area of health psychology, on the basis of researches done in the Web of Science, PubMed and Scopus databases.

Este trabajo presenta una visión panorámica de la producción y del acceso a la información científica en publicaciones periódicas en el campo de la psicología en Portugal. Desde el punto de vista de la producción, es hecho un inventario de las publicaciones periódicas editadas en Portugal, en formato electrónico, su distribución o pubicación en portales o sitios de la Web. Desde el punto de vista del acceso, se indica las bases de datos y las publicaciones periódicas disponibles, quien puede tener acceso a ellas y como hacerlo. Se da destaque al proyecto B-On (Biblioteca del Conocimiento Online). Se analiza la accesibilidad de los periódicos con impacto más fuerte para la psicología en general y son fornecidos algunos datos para el área más específica de la psicología de la salud, con base en investigaciones efectuadas en las bases de datos Web of Science, PubMed y Scopus.

Produção e acesso a fontes de informação para a psicologia em Portugal

ResumoEste trabalho faz uma panorâmica da produção e do acesso à informação científica em publicações periódicas no campo da psicologia, em Portugal. Do ponto de vista da produção, é feito um inventário das publicações periódicaseditadas em Portugal em formato electrónico e sua distribuição ou alojamento em portais ou websites. Do ponto de vista do acesso, que bases de dados, que publicações periódicas estão disponíveis, para quem e como podem ser acedidas. Faz-se um destaque para o projecto B-On (Biblioteca do Conhecimento Online). Analisa-se a acessibilidade dos periódicos com maior impacto para a psicologia em geral e são fornecidos alguns dados para a área mais específica da psicologia da saúde, com base em pesquisas efectuadas nas bases de dados Web of Science, PubMed e Scopus. (AU)

This paper presents a panoramic view of the production and access to scientific information in periodical publications in the field of psychology in Portugal. From the point of view of production, an inventory of the periodical publications published in Portugal in electronic format, its distribution or hosting in portals or websites is made. From the point of view of access it is indicated the databases and the periodical publications available, who can have access to them and how to do it. It is highlighted the B-On project (Biblioteca do Conhecimento Online, that is, Online Knowledge Library). It is also analyzed the accessibility to the periodicals with greatest impact for general psychology and are provided some data for the More specific area of health psychology, on the basis of researches done in the Web of Science, PubMed and Scopus databases. (AU)

Este trabajo presenta una visión panorámica de la producción y del acceso a la información científica en publicaciones periódicas en el campo de la psicología en Portugal. Desde el punto de vista de la producción, es hecho un inventario de las publicaciones periódicas editadas en Portugal, en formato electrónico, su distribución o pubicación en portales o sitios de la Web. Desde el punto de vista del acceso, se indica las bases de datos y las publicaciones periódicas disponibles, quien puede tener acceso a ellas y como hacerlo. Se da destaque al proyecto B-On (Biblioteca del Conocimiento Online). Se analiza la accesibilidad de los periódicos con impacto más fuerte para la psicología en general y son fornecidos algunos datos para el área más específica de la psicología de la salud, con base en investigaciones efectuadas en las bases de datos Web of Science, PubMed y Scopus. (AU)

Comparative study of the prereactive protein kinase A Michaelis complex with kemptide substrate.

In the present work we have modeled the Michaelis complex of the cyclic-Adenosine Monophosphate Dependent (cAMD) Protein Kinase A (PKA) with Mg(2)ATP and the heptapeptide substrate Kemptide by classical molecular dynamics. The chosen synthetic substrate is relevant for its high efficiency and small size, and it has not been used in previous theoretical studies. The structural analysis of the data generated along the 6 ns simulation indicates that the modeled substrate-enzyme complex mimics the substrate binding pattern known for PKA. The values of the average prereactive distances obtained from the simulation do not exclude any of the two limiting situations proposed as mechanisms in the literature for the phosphorylation reaction (dissociative and associative) because the system oscillates between configurations compatible with each of them. Furthermore, the results obtained for the average interaction distances between active site residues concord in suggesting the plausibility of an alternative third reaction mechanism.

Financiamento de pesquisa / Research financing

Mesa redonda onde se discute a situaçäo atual, as preocupaçöes, os problemas e as sugestöes visando resolver a questäo do financiamento da pesquisa. Participaram representantes da FINEP, FAPESP, DCTEC e OPAS (AMSB)