Cyclin-Dependent Kinase 2 in Cellular Senescence and Cancer. A Structural and Functional Review.

BACKGROUND: Cyclin-dependent kinase 2 (CDK2) has been studied due to its role in the cell-cycle progression. The elucidation of the CDK2 structure paved the way to investigate the molecular basis for inhibition of this enzyme, with the coordinated efforts combining crystallography with functional studies. OBJECTIVE: Our goal here is to review recent functional and structural studies directed to understanding the role of CDK2 in cancer and senescence. METHODS: There are over four hundreds of crystallographic structures available for CDK2, many of them with binding affinity information. We use this abundance of data to analyze the essential features responsible for the inhibition of CDK2 and its function in cancer and senescence. RESULTS: The structural and affinity data available CDK2 makes it possible to have a clear view of the vital CDK2 residues involved in molecular recognition. A detailed description of the structural basis for ligand binding is of pivotal importance in the design of CDK2 inhibitors. Our analysis shows the relevance of the residues Leu 83 and Asp 86 for binding affinity. The recent findings revealing the participation of CDK2 inhibition in senescence open the possibility to explore the richness of structural and affinity data for a new era in the development of CDK2 inhibitors, targeting cellular senescence. CONCLUSION: Here, we analyzed structural information for CDK2 in combination with inhibitors and mapped the molecular aspects behind the strongest CDK2 inhibitors for which structures and ligandbinding affinity data were available. From this analysis, we identified the significant intermolecular interactions responsible for binding affinity. This knowledge may guide the future development of CDK2 inhibitors targeting cancer and cellular senescence.

Avaliação da susceptibilidade e resistência bacteriana aos agentes controladores do crescimento de uso hospitalar e industrial / Bacterial susceptibility and resistance to growth controlling agents in hospital and industrial use

O presente trabalho tem como objetivo estudar o comportamento e a resistência de bactérias em relação a agentes químicos com ação antimicrobiana em diferentes concentrações e determinar a quantidade mínina para que ocorra a inibição dos microrganismos. Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosas, Escherichia coli, Bacillus cereus e Staphylococcus aureus, foram os microrganismos utilizados, os quais foram semeados em meio Plate Count Agar (PCA). Na sequência, aplicaram-se os testes com os agentes controladores, nas concentrações de 0,5 %, 1,5%, 3,0%, 5,0%, 7,0% e 10,0 %, e os álcoois pré-determinados. A identificação da eficácia foi definida atraves frequência e índice de inibição. Foram realizadas análises de 13 substâncias nas seis diferentes concentrações, ou seja, 468 amostras totalizadas no experimento. Com relação aos microrganismos estudados observou-se, dentre os componentes escolhidos, uma ampla resistência, mesmo em concentrações maiores. O estudo demonstrou variação de resistência e sensibilidade, sendo ácido ascórbico o agente com a maior concentração inibitória mínima e as menores concentrações foram do peróxido de hidrogênio. Considerando importância do uso desses compostos na inibição e no controle de agentes bacterianos em diferentes áreas, torna-se vital o conhecimento da amplitude de seu espectro, assim, alguns produtos, nas diluições recomendadas para uso, revelaram possuir atividade antibacteriana mais reduzida ou inexistente.

The present work aims at studying the behavior and bacteria resistance against chemical agents with antimicrobial action in different concentrations and determining the minimum quantity for micro-organism inhibition. This study used Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus and Staphylococcus aureus micro-organisms, which were seeded in Plate Count Agar (PCA) medium. After, the tests were applied with controlling agents, at concentrations of 0.5%, 1.5%, 3.0%, 5.0%, 7.0% and 10.0%, and predetermined alcohols. Effectiveness was identified by frequency and inhibition index. Analyses were carried out on 13 substances in six different concentrations, i.e., a total of 468 samples in the experiment. In relation to the studied micro-organism, a broad resistance could be observed among the chosen components, even in larger concentrations. The study presented resistance and sensitivity variation, with ascorbic acid being the agent with the greatest minimum inhibitory concentration, while hydrogen peroxide presented the lowest concentrations. Considering the importance of these compounds in inhibiting and controlling bacterial agents in different areas, it is vital to expand the knowledge on the broadness of its spectrum, since some of the products, at the recommended use dilutions, presented low or non-existent antibacterial activity.