title: Protein prosthesis: a nonnatural residue accelerates folding and increases stability.
abstract: Nonnatural residues can endow proteins with desirable properties. Here, replacing a proline residue that has a cis peptide bond in native ribonuclease A with 5,5-dimethyl-l-proline is shown to accelerate protein folding by 6-fold and enhance conformational stability by DeltaTm = 2.8 +/- 0.3 degrees C while having no effect on enzymatic activity. The rational use of this and other prosthetic segments could enable chemotherapeutic proteins to survive longer in vivo or retain activity after oral administration.
authors.affiliation: Department of Biochemistry/Biotechnology, Martin-Luther University, 06099 Halle, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Arnold
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hinderaker
authors.forename: Jens
authors.initials: J
authors.lastname: Köditz
authors.forename: Ralph
authors.initials: R
authors.lastname: Golbik
authors.forename: Renate
authors.initials: R
authors.lastname: Ulbrich-Hofmann
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D007700:Kinetics; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D017510:Protein Folding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D011392:Proline; D012259:Ribonuclease, Pancreatic; C003342:stachydrine