title: Mitogen-activated protein kinase 4 of Leishmania parasite as a therapeutic target.
abstract: 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.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Saravanan
authors.forename: Santhosh K
authors.initials: SK
authors.lastname: Venkatesan
authors.forename: C Gopi
authors.initials: CG
authors.lastname: Mohan
authors.forename: Sanjukta
authors.initials: S
authors.lastname: Patra
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Dubey
mesh_terms: D000595:Amino Acid Sequence; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007894:Leishmania mexicana / Q000201:enzymology*; D008024:Ligands; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; C535150:MAPK1 protein, human; C102548:Mapk4 protein, rat; D019950:Mitogen-Activated Protein Kinase 1