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Estrutura Tridimensional da Major Surface Protease de Leishmania guyanensis Resolvida por Modelagem Comparativa

DOI: http://dx.doi.org/10.18561/2179-5746/biotaamazonia.v4n1p74-80

http://periodicos.unifap.br/index.php/biota/index 

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Paulo H. M. Calixto1, Diego S. Fagundes2 & Júlio C. S. de Oliveira3

 

Resumo: O objetivo deste trabalho foi gerar e caracterizar a estrutura tridimensional da Major Surface Protease (MSP) de L. guyanensis (LgMSP). A obtenção do modelo estrutural foi realizada por modelagem comparativa, empregando o programa Modeller, a partir da sequência de aminoácidos da LgMSP depositada no GenBank. Os resultados obtidos apontaram que a LgMSP possui todos os elementos necessários para o processamento póstraducional e de funcionamento, tais como: peptídeo sinal; pro-peptídeo; sinal de adição da âncora de glicosilfostatidilinositol (GPI); e os aminoácidos envolvidos na composição do sítio catalítico, motif HEXXH. A estrutura da LgMSP, apresentou as mesmas características estruturais da proteína molde, MSP de Leishmania major (LmMSP). O alinhamento entre as estruturas de LgMSP e LmMSP revelou grande conservação estrutural, sobretudo dos subdomínios onde está localizado o sítio catalítico. O estudo das cargas parciais aponta a mesma distribuição das cargas de superfície, indicando que ambas as proteínas possam clivar os mesmos substratos. De acordo com os  resultados, sugerimos que a LgMSP seja um excelente alvo para o tratamento profilático e/ou curativo da leishmaniose tegumentar americana, através do desenho racional de fármacos baseado na estrutura gerada.

Palavras-chave: MSP, modelagem comparativa, Leishmania guyanensis, estrutura, cargas de superfície, conservação estrutural.

 

Abstract: The objective of this study was to generate and characterize the three-dimensional structure of L. guyanensis Major Surface Protease (LgMSP). The generation of the structural model was performed by comparative modeling, using the program Modeller from the amino acid sequence LgMSP deposited in GenBank. The results showed that the LgMSP has all the elements necessary for the post-translational processing and functionality, such as signal peptide, propeptide; addition signal glicosilfostatidilinositol anchor (GPI) and the amino acids involved in the composition of catalytic site, HEXXH motif. The structure of LgMSP, showed the same structural characteristics of the  template-protein, Major Surface Protease Leishmania major (LmMSP). The alignment between the structures Lg MSP and LmMSP revealed great structural conservation, especially the subdomains where is located the catalytic site. The study of the partial charges shows the same distribution of surface charges, indicating that both proteins can cleave the same substrates. According to the results suggest that LgMSP is an excellent target for the prophylactic and/or curative treatment of American tegumentary leishmaniasis, through rational drug design based on structure generated.

Key words: MSP; comparative modeling; Leishmania guyanensis; structure; surface charges; structural conservation.

 

1 Professor da Universidade Federal do Amapá, Campus Binacional Oiapoque, NEPA - Núcleo de Estudos em Pesca e Aquicultura. E-mail: matayoshi@unifap.br
2 Universidade Federal do Amapá. Campus Binacional Oiapoque. NEPA - Núcleo de Estudos em Pesca e Aquicultura. E-mail: diegosfagundes@unifap.br
3 Universidade Federal do Amapá. Campus Marco Zero. NEPA - Núcleo de Estudos em Pesca e Aquicultura. E-mail: juliosa@unifap.br

 

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