title: Solution structures of human transforming growth factor alpha derived from 1H NMR data.
abstract: The 600-MHz 1H NMR spectrum of the des-Val-Val mutant of human transforming growth factor alpha (TGF-alpha) was reassigned at pH = 6.3. The conformation space of des-Val-Val TGF-alpha was explored by distance geometry embedding followed by restrained molecular dynamics refinement using NOE distance constraints and some torsion angle constraints derived from J-couplings. Over 80 long-range NOE constraints were found by completely assigning all resolved cross-peaks in the NOESY spectra. Low NOE constraint violations were observed in structures obtained with the following three different refinement procedures: interactive annealing in DSPACE, AMBER 3.0 restrained molecular dynamics, and dynamic simulated annealing in XPLOR. The segment from Phe15 to Asp47 was found to be conformationally well-defined. Back-calculations of NOESY spectra were used to evaluate the quality of the structures. Our calculated structures resemble the ribbon diagram presentations that were recently reported by other groups. Several side-chain conformations appear to be well-defined as does the relative orientation of the C loop to the N-terminal half of the protein.
authors: Smith Kline & French Laboratories, King of Prussia, Pennsylvania 19406-0939.
authors: T P
authors: TP
authors: Kline
authors: F K
authors: FK
authors: Brown
authors: S C
authors: SC
authors: Brown
authors: P W
authors: PW
authors: Jeffs
authors: K D
authors: KD
authors: Kopple
authors: L
authors: L
authors: Mueller
mesh_terms: D003198:Computer Simulation; D006801:Humans; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D012996:Solutions; D013237:Stereoisomerism; D016211:Transforming Growth Factor alpha / Q000737:chemistry* / Q000235:genetics
chemical_list: D012996:Solutions; D016211:Transforming Growth Factor alpha; D006859:Hydrogen