Design of miniproteins by the transfer of active sites onto small-size scaffolds.
Methods Mol Biol
; 340: 113-49, 2006.
Article
em En
| MEDLINE
| ID: mdl-16957335
ABSTRACT
Natural miniproteins (e.g., animal toxins, protease inhibitors, defensins) can express specific and powerful biological activities by using a stable and minimal (<80 amino acids) structural motif. Artificial activities have been designed on these miniscaffolds by transferring previously identified protein active sites into regions structurally compatible with the site and permissive for sequence mutations. These newly designed miniproteins, presenting a specific and high activity within a small size and well-defined three-dimensional structure, represent novel tools in biology, biotechnology, and medical sciences, and are also useful intermediates to develop new therapeutic agents. The different steps used to design and characterize new bioactive miniproteins are here described in detail. Two successful examples are here reported. The first one is a metal-binding miniprotein (MBP, 37 residues), which possesses a metal specificity resembling that of natural carbonic anhydrase; the second is a CD4 mimic (CD4M33, 27 residues), which is a powerful inhibitor of HIV-1 entry but also a fully functional substitute of the human receptor CD4 and, hence, a potential component of an AIDS vaccine.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
/
Modelos Moleculares
/
Antígenos CD4
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Dobramento de Proteína
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Mimetismo Molecular
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article