title: Homology modeling and molecular dynamics study of NAD-dependent glycerol-3-phosphate dehydrogenase from Trypanosoma brucei rhodesiense, a potential target enzyme for anti-sleeping sickness drug development.
abstract: Sleeping sickness and Chagas disease are among the most severe diseases in Africa as well as Latin America. These two diseases are caused by Trypanosoma spp. Recently, an enzyme of a glycolytic pathway, NAD-dependent glycerol-3-phosphate dehydrogenase, of Leishmania mexicana was crystallized and its structure determined by x-ray crystallography. This structure has offered an excellent template for modeling of the homologous enzymes from another Trypanosoma species. Here, a homology model of the T. brucei enzyme based on the x-ray structure of LmGPDH has been generated. This model was used as the starting point for molecular dynamics simulation in a water box. The analysis of the molecular dynamics trajectory indicates that the functionally important motifs have both a very stable secondary structure and tertiary arrangement.
authors.affiliation: Department of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South Africa. i.zubrzycki@ru.ac.za
authors.forename: Igor Z
authors.initials: IZ
authors.lastname: Zubrzycki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D015195:Drug Design; D004795:Enzyme Stability; D005993:Glycerolphosphate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007894:Leishmania mexicana / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013816:Thermodynamics; D016833:Trypanosoma brucei rhodesiense / Q000201:enzymology* / Q000235:genetics; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000469:parasitology
chemical_list: D009243:NAD; D005993:Glycerolphosphate Dehydrogenase