Estudos estruturais da Purina Nucleosídeo Fosforilase do Mycobacterium tuberculosis complexada com ligantes
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2007-02-23
Autores
Souza, Marcos Michel de [UNESP]
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Universidade Estadual Paulista (Unesp)
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De acordo com a OMS, a tuberculose mata 5000 pessoas por dia, e se não controlada, são estimados 35 milhões de novos casos nos próximos vinte anos. A alta susceptibilidade dos infectados por HIV para a tuberculose, bem como a proliferação da tuberculose multidroga-resistente (MDR), tem criado um grande interesse mundial de expansão nos programas atuais de pesquisas sobre a tuberculose. A Purina Nucleosídeo Fosforilase do Mycobacterium tuberculosis (MtPNP) é um potencial alvo para novas drogas anti-tuberculose visto que é responsável pela síntese de novo de ribonucleotídeos de purina. A Inibição específica da PNP poderia potencialmente levar o M. tuberculosis ao estado latente. O objetivo desde trabalho é resolver a estrutura da MtPNP complexada com adenina, e analisar as interações com os ligantes. A MtPNP foi cristalizada utilizando condições experimentais descritas posteriormente, e o ligante (adenina) foi adicionado por soaking. Os dados de difração de raios X foram coletados no detector CCD utilizando fonte de radiação síncotron (Laboratório Nacional de Luz Síncrotron, LNLS, Campinas, Brazil). O programa MOSFLM foi utilizado para o processamento, e os dados foram escalonados através do programa SCALA, apresentando o grupo espacial ortorrômico P21212 (a=118,96Å, b=134,65 Å, c=44,42 Å). O cristal foi determinado utilizando o método de substituição...
In according to the WHO, the tuberculosis kills 5000 people every day, if does not controlled, are esteemed 35 millions of new cases in next 20 years. The high susceptibility of human immunodeficiency virus infected persons to the disease and the proliferation of multidrug-resistant (MDR) strains have created a worldwide interest in expanding current programs in tuberculosis research. The Purine Nucleoside Phosphorylase from Mycobacterum tuberculosis (MtPNP) is a potential target for new drug anti-tuberculosis, whereas is responsible for de novo synthesis of purine ribonucleotides. The specific inhibition of M. tuberculosis PNP could potentially lead to the latent state of M. tuberculosis. The objective of this work is to solve the structure from MtPNP complexed with adenine, and to analyze their interactions with the ligand. MtPNP was crystallized using the experimental conditions described elsewhere, and the ligand (adenine) was added by soaking. The X-ray diffraction data were collected on a CCD detector using synchrotron radiation source (Laboratório Nacional de Luz Síncrotron, LNLS, Campinas, Brazil). It was used the MOSFLM program to processing, and the data were scaled through the program SCALA, presenting orthorhombic spatial group P21212 (a=118,96Å, b=134,65 Å, c=44,42 Å). The crystal was determined by molecular replacement methods using the program AMoRe. The final model has Rfree and Rfactor of 23.87% and 17.51% respectively, and maximum resolution of 1.86Å. It was observed a large...(Complete abstract click electronic access below)
In according to the WHO, the tuberculosis kills 5000 people every day, if does not controlled, are esteemed 35 millions of new cases in next 20 years. The high susceptibility of human immunodeficiency virus infected persons to the disease and the proliferation of multidrug-resistant (MDR) strains have created a worldwide interest in expanding current programs in tuberculosis research. The Purine Nucleoside Phosphorylase from Mycobacterum tuberculosis (MtPNP) is a potential target for new drug anti-tuberculosis, whereas is responsible for de novo synthesis of purine ribonucleotides. The specific inhibition of M. tuberculosis PNP could potentially lead to the latent state of M. tuberculosis. The objective of this work is to solve the structure from MtPNP complexed with adenine, and to analyze their interactions with the ligand. MtPNP was crystallized using the experimental conditions described elsewhere, and the ligand (adenine) was added by soaking. The X-ray diffraction data were collected on a CCD detector using synchrotron radiation source (Laboratório Nacional de Luz Síncrotron, LNLS, Campinas, Brazil). It was used the MOSFLM program to processing, and the data were scaled through the program SCALA, presenting orthorhombic spatial group P21212 (a=118,96Å, b=134,65 Å, c=44,42 Å). The crystal was determined by molecular replacement methods using the program AMoRe. The final model has Rfree and Rfactor of 23.87% and 17.51% respectively, and maximum resolution of 1.86Å. It was observed a large...(Complete abstract click electronic access below)
Descrição
Palavras-chave
Biologia molecular, Cristalografia, Proteínas - Estrutura, Mycobacterium tuberculosis, Biofísica molecular, Purinas - Estrutura, Purina nucleosídeo fosforilase, PNP (Enzimas), MtPNP (Enzimas)
Como citar
SOUZA, Marcos Michel de. Estudos estruturais da Purina Nucleosídeo Fosforilase do Mycobacterium tuberculosis complexada com ligantes. 2007. 86 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências, Letras e Ciências Exatas, 2007.