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

ABSTRACT: 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.

SUBMITTER: Junior MC 

PROVIDER: S-EPMC3610160 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature