Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone activity.
Proc Natl Acad Sci U S A
; 111(32): 11679-84, 2014 Aug 12.
Article
en En
| MEDLINE
| ID: mdl-25071217
ABSTRACT
Mirror-image proteins (composed of D-amino acids) are promising therapeutic agents and drug discovery tools, but as synthesis of larger D-proteins becomes feasible, a major anticipated challenge is the folding of these proteins into their active conformations. In vivo, many large and/or complex proteins require chaperones like GroEL/ES to prevent misfolding and produce functional protein. The ability of chaperones to fold D-proteins is unknown. Here we examine the ability of GroEL/ES to fold a synthetic d-protein. We report the total chemical synthesis of a 312-residue GroEL/ES-dependent protein, DapA, in both L- and D-chiralities, the longest fully synthetic proteins yet reported. Impressively, GroEL/ES folds both L- and D-DapA. This work extends the limits of chemical protein synthesis, reveals ambidextrous GroEL/ES folding activity, and provides a valuable tool to fold d-proteins for drug development and mirror-image synthetic biology applications.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pliegue de Proteína
/
Chaperonas Moleculares
/
Enzimas
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2014
Tipo del documento:
Article