Mitogen-activated protein kinase 4 of Leishmania parasite as a therapeutic target

作者:Saravanan Parameswaran; Venkatesan Santhosh K; Mohan C Gopi; Patra Sanjukta*; Dubey Vikash Kumar
来源:European Journal of Medicinal Chemistry, 2010, 45(12): 5662-5670.
DOI:10.1016/j.ejmech.2010.09.020

摘要

Protein kinases are important regulators of many different cellular processes such as transcriptional control, cell cycle progression and differentiation, and have drawn much attention as potential drug targets. Leishmania mexicana mitogen-activated protein kinase 4 (LmxMPK4) is crucial for the survival of the parasite. As the crystal structure of the enzyme is not known, we have used bioinformatics techniques to model LmxMPK4 structure. The current study reveals conservation of all sequence and structural motifs of LmxMPK4. Study shows mitogen-activated protein kinases are highly conserved throughout different Leishmania species and significant divergence is observed towards mammalian mitogen-activated protein kinases. Additionally, using virtual docking methods, we have identified inhibitors for LmxMPK4. The sequence and structure analysis results were helpful in identifying the ligand binding sites and molecular function of the Leishmania specific mitogen-activated protein kinase.