Structure-based drug design studies of UDP-N-acetylglucosamine pyrophosphosrylase, a key enzyme for the control of witches’ broom disease

Chemistry Central Journal

Manoelito C Santos Junior⁵  Sandra Aparecida de Assis⁵  Aristóteles Góes-Neto¹  Ângelo Amâncio Duarte²  Ricardo José Alves³  Moacyr Comar Junior⁴  Alex Gutterres Taranto⁴ 

[1] Ciências Biológicas, Feira de Santana, Feira de Santana-BA 44031-460, Brazil

[2] Tecnologia, Programa de Pós-Graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana-BA 44031-460, Brazil

[3] Universidade Federal de Minas Gerais, Faculdade de Farmácia, Departamento de Produtos Farmacêuticos, Av. Antônio Carlos, 6627, Pampulha 31270-901, Belo Horizonte, MG, Brazil

[4] Laboratório de Modelagem Molecular, Programas de Pós-Graduação em Biotecnologia e Ciências Farmacêuticas, Campus Centro Oeste (CCO), Universidade Federal de São João Del-Rei, Divinópolis-MG 35501-296, Brazil

[5] Departamentos de Saúde, Feira de Santana, Feira de Santana-BA 44031-460, Brazil

关键词: Moniliophthora perniciosa;    Pyrophosphorylase;    Molecular dynamics;    Docking;   

Others  :  787944
DOI  :  10.1186/1752-153X-7-48

 received in 2012-12-06, accepted in 2013-02-15,  发布年份 2013

【 摘 要 】

Background

The witches’ broom disease is a plague caused by Moniliophthora perniciosa in the Theobroma cacao, which has been reducing the cocoa production since 1989. This issue motivated a genome project that has showing several new molecular targets, which can be developed inhibitors in order to control the plague. Among the molecular targets obtained, the UDP-N-acetylglucosamine pyrophosphorylase (UNAcP) is a key enzyme to construct the fungal cell wall. The inhibition of this enzyme results in the fungal cell death.

Results

The results show that the molecular recognition of the enzyme with the substrates occurs mainly by hydrogen bonds between ligands and Arg116, Arg383, Gly381, and Lys408 amino acids; and few hydrophobic interactions with Tyr382 and Lys123 residues.

Conclusions

Among the compounds analyzed, the NAG5 showed the best binding energy (−95.2 kcal/mol). The next steps for the control of witches’ broom plague involve the synthesis and biological evaluation of these compounds, which are in progress.

【 授权许可】

   
2013 Junior et al.; licensee Chemistry Central Ltd.

【 图 表 】

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