Protein prosthesis: a nonnatural residue accelerates folding and increases stability.
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.
Arnold
Ulrich
U
Department of Biochemistry/Biotechnology, Martin-Luther University, 06099 Halle, Germany.
Hinderaker
Matthew P
MP
Köditz
Jens
J
Golbik
Ralph
R
Ulbrich-Hofmann
Renate
R
Raines
Ronald T
RT
D007700:Kinetics; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D017510:Protein Folding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry*; D013816:Thermodynamics
D011392:Proline; D012259:Ribonuclease, Pancreatic; C003342:stachydrine