Design and engineering of an O(2) transport protein.
Nature
; 458(7236): 305-9, 2009 Mar 19.
Article
en En
| MEDLINE
| ID: mdl-19295603
ABSTRACT
The principles of natural protein engineering are obscured by overlapping functions and complexity accumulated through natural selection and evolution. Completely artificial proteins offer a clean slate on which to define and test these protein engineering principles, while recreating and extending natural functions. Here we introduce this method with the design of an oxygen transport protein, akin to human neuroglobin. Beginning with a simple and unnatural helix-forming sequence with just three different amino acids, we assembled a four-helix bundle, positioned histidines to bis-histidine ligate haems, and exploited helical rotation and glutamate burial on haem binding to introduce distal histidine strain and facilitate O(2) binding. For stable oxygen binding without haem oxidation, water is excluded by simple packing of the protein interior and loops that reduce helical-interface mobility. O(2) affinities and exchange timescales match natural globins with distal histidines, with the remarkable exception that O(2) binds tighter than CO.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oxígeno
/
Ingeniería de Proteínas
/
Proteínas Portadoras
Límite:
Humans
Idioma:
En
Revista:
Nature
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos