title: Synthetic, structural and biological studies of the ubiquitin system: chemically synthesized and native ubiquitin fold into identical three-dimensional structures.
abstract: The solid-phase chemical synthesis of ubiquitin produced a molecule with physicochemical properties similar to those of the natural protein. We have grown crystals of this synthetic ubiquitin and performed an X-ray analysis at 1.8 A resolution in order to compare the synthetic protein with the known natural structure. The crystals were isomorphous with those of the natural protein, the R-factor between them being 7.1%. Difference Fourier analysis shows that the synthetic and natural structures are indistinguishable. The co-ordinates of the natural ubiquitin (1UBQ) were used as the starting point for restrained least-squares refinement (TNT program) against the synthetic X-ray data. The refinement converged to R = 16.5% and the resulting model did not change when refined against natural ubiquitin X-ray data (R = 18.7%). From both the refinement and featureless difference Fourier synthesis, we conclude that the synthetic and natural protein structures are identical. A short discussion about the uses of proteins with 'non-standard' amino acid residues is included.
authors.affiliation: Edinburgh Centre for Molecular Recognition, Department of Biochemistry, University of Edinburgh, Scotland, U.K.
authors.forename: D
authors.initials: D
authors.lastname: Alexeev
authors.forename: S M
authors.initials: SM
authors.lastname: Bury
authors.forename: M A
authors.initials: MA
authors.lastname: Turner
authors.forename: O M
authors.initials: OM
authors.lastname: Ogunjobi
authors.forename: T W
authors.initials: TW
authors.lastname: Muir
authors.forename: R
authors.initials: R
authors.lastname: Ramage
authors.forename: L
authors.initials: L
authors.lastname: Sawyer
mesh_terms: D018360:Crystallography, X-Ray; D011487:Protein Conformation; D017510:Protein Folding; D014452:Ubiquitins / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D014452:Ubiquitins