title: The malarial drug target Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR): development of a 3-D model for identification of novel, structural and functional features and for inhibitor screening.
abstract: A three-dimensional model of the malarial drug target protein PfDXR was generated, and validated using structure-checking programs and protein docking studies. Structural and functional features unique to PfDXR were identified using the model and comparative sequence analyses with apicomplexan and non-apicomplexan DXR proteins. Furthermore, we have used the model to develop an efficient approach to screen for potential tool compounds for use in the rational design of novel DXR inhibitors.
authors.affiliation: Biomedical Biotechnology Research Unit, Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown 6140, South Africa.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Goble
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Adendorff
authors.forename: Tjaart A P
authors.initials: TA
authors.lastname: de Beer
authors.forename: Linda L
authors.initials: LL
authors.lastname: Stephens
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Blatch
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005578:Fosfomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D011485:Protein Binding; D015203:Reproducibility of Results; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D005578:Fosfomycin; C024640:fosmidomycin; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases