title: Molecular and structural insight into plasmodium falciparum RIO2 kinase.
abstract: Among approximately 65 kinases of the malarial genome, RIO2 (right open reading frame) kinase belonging to the atypical class of kinase is unique because along with a kinase domain, it has a highly conserved N-terminal winged helix (wHTH) domain. The wHTH domain resembles the wing like domain found in DNA binding proteins and is situated near to the kinase domain. Ligand binding to this domain may reposition the kinase domain leading to inhibition of enzyme function and could be utilized as a novel allosteric site to design inhibitor. In the present study, we have generated a model of RIO2 kinase from Plasmodium falciparum utilizing multiple modeling, simulation approach. A novel putative DNA-binding site is identified for the first time in PfRIO2 kinase to understand the DNA binding events involving wHTH domain and flexible loop. Induced fit DNA docking followed by minimization, molecular dynamics simulation, energetic scoring and binding mode studies are used to reveal the structural basis of PfRIO2-ATP-DNA complex. Ser105 as a potential site of phosphorylation is revealed through the structural studies of ATP binding in PfRIO2. Overall the present study discloses the structural facets of unknown PfRIO2 complex and opens an avenue toward exploration of novel drug target.
authors.affiliation: Department of Applied Chemistry, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Chouhan
authors.forename: Ashoke
authors.initials: A
authors.lastname: Sharon
authors.forename: Chandralata
authors.initials: C
authors.lastname: Bal
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D019843:Archaeal Proteins / Q000737:chemistry; D019611:Archaeoglobus fulgidus / Q000737:chemistry / Q000201:enzymology; D001665:Binding Sites; D016054:DNA, Protozoan / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019077:Helix-Turn-Helix Motifs; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000737:chemistry / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000201:enzymology; D016415:Sequence Alignment; D012694:Serine / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D019843:Archaeal Proteins; D016054:DNA, Protozoan; D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; D012694:Serine; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases