title: Protein structure determination using a combination of comparative modeling and NMR spectroscopy. Application to the response regulator protein, Spo0F.
abstract: A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obtained by this method are suitable for drug discovery. The results of the GRID and DOCK methods as applied to the model and X-ray structures of Spo0F are remarkably similar and tend to suggest the same design conclusions. This trend is illustrated by these same techniques applied to two experimentally derived structures of the analogous protein, CheY, which exhibit a pairwise rmsdBB on the same order as that found for the two Spo0F structures.
authors.affiliation: R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Podlogar
authors.forename: G C
authors.initials: GC
authors.lastname: Leo
authors.forename: P A
authors.initials: PA
authors.lastname: McDonnell
authors.forename: D A
authors.initials: DA
authors.lastname: Loughney
authors.forename: G W
authors.initials: GW
authors.lastname: Caldwell
authors.forename: J F
authors.initials: JF
authors.lastname: Barrett
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D002633:Chemotaxis / Q000502:physiology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010770:Phosphotransferases / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012984:Software
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; C080951:Spo0F protein, Bacillus subtilis; D010770:Phosphotransferases