title: Computer modeling of small heat-shock metalloprotease of the human malaria parasite Plasmodium vivax.
abstract: We present here computer generated model of N-terminal fragment, amino acids (aa) 36-245, of a Plasmodium vivax heat shock metalloprotease called PVHSP28, whose gene was cloned and characterised earlier. The fragment showed homology with HSPs from many organisms, including Escherichia coli and Haemophilus influenzae. PVHSP28 had the signature sequence 'HEXXH' and 'EXXXD' of Zinc metalloproteases. Being the first malarial HSP possessing metalloprotease activity, PVHSP28 is an ideal target for the design of new anti-malarial drugs. However, except for a small region (aa 62-132) which had 24.6% sequence similarity with 1TAQ (a DNA polymerase), it did not show sequence similarity with any published structures in protein data bank. Hence it could not be modelled using any automated modeling programs. We modelled 36-245 aa of PVHSP28 using predicted secondary structure as well as experimentally determined and predicted properties of the protein on the basis of its amino acid sequence, using various Internet tools and in-house package MODEL. The model was energy minimised using Sander's module of AMBER 5.0, working on a Silicon Graphics machine, with all atom force field.
authors.affiliation: Department of Biophysics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi. kothekar@hotmail.com
authors.forename: V
authors.initials: V
authors.lastname: Kothekar
authors.forename: S
authors.initials: S
authors.lastname: Shankar
authors.forename: S
authors.initials: S
authors.lastname: Lomash
authors.forename: Y D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010966:Plasmodium vivax / Q000201:enzymology* / Q000235:genetics; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics; D013816:Thermodynamics
chemical_list: D006360:Heat-Shock Proteins; D008051:Lipid Bilayers; D015800:Protozoan Proteins; D008666:Metalloendopeptidases; C111473:PV9 protein, Plasmodium vivax