Homology modeling and molecular dynamics study of chorismate synthase from Shigella flexneri

Journal of Molecular Graphics & Modelling
Hong ZhouKwang S Kim

Abstract

Shigellosis is a major public health problem in many developing countries. Antibiotic therapy can reduce the severity of the dysentery and prevent potentially lethal complication. However, owing to the increased resistance to most of the widely used and inexpensive antibiotics, there is an urgent need for new antibacterial agents, particularly those that act on novel targets. Chorismate synthase (CS) is a key enzyme in the shikimic acid pathway, which is essential for the synthesis of aromatic amino acids in bacteria. As an anti-bacterial drug target, CS has been well validated. A homology model of Shigella-CS with the flavin mononucleotide (FMN) binding was constructed using the crystal structure of CS from other species. The substrate 5-enolpyruvylshikimate 3-phosphate (EPSP) was subsequently docked into the active site based on previous theoretical studies. Molecular dynamics (MD) was used to refine the starting ternary model. The model was well conserved during the 1.8 ns MD simulation with the equilibrium root mean square deviation (RMSD) value of 3.5 angstrom. The substrate binding energy was calculated and the electrostatic energy was found to be the most important term for binding. Decomposition of binding energies reve...Continue Reading

References

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Apr 21, 2004·Journal of Molecular Biology·Hyung Jun AhnSe Won Suh
Aug 28, 2004·Journal of Molecular Graphics & Modelling·Heejung YangYoongho Lim
Jul 28, 2005·Journal of Molecular Graphics & Modelling·Youyi PengWilliam J Welsh

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Citations

Jul 27, 2010·Interdisciplinary Sciences, Computational Life Sciences·Neelima AroraU S N Murty
Dec 4, 2012·Indian Journal of Pharmaceutical Sciences·V K VyasC Chintha

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