作者
Claudio Vita, Eugenia Drakopoulou, Jean Vizzavona, Sandrine Rochette, Loïc Martin, André Ménez, Christian Roumestand, Yin-Shan Yang, Loyda Ylisastigui, Abdelaziz Benjouad, Jean Claude Gluckman
发表日期
1999/11/9
期刊
Proceedings of the National Academy of Sciences
卷号
96
期号
23
页码范围
13091-13096
出版商
The National Academy of Sciences
简介
Protein–protein interacting surfaces are usually large and intricate, making the rational design of small mimetics of these interfaces a daunting problem. On the basis of a structural similarity between the CDR2-like loop of CD4 and the β-hairpin region of a short scorpion toxin, scyllatoxin, we transferred the side chains of nine residues of CD4, central in the binding to HIV-1 envelope glycoprotein (gp120), to a structurally homologous region of the scorpion toxin scaffold. In competition experiments, the resulting 27-amino acid miniprotein inhibited binding of CD4 to gp120 with a 40 μM IC50. Structural analysis by NMR showed that both the backbone of the chimeric β-hairpin and the introduced side chains adopted conformations similar to those of the parent CD4. Systematic single mutations suggested that most CD4 residues from the CDR2-like loop were reproduced in the miniprotein, including the critical Phe …
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C Vita, E Drakopoulou, J Vizzavona, S Rochette… - Proceedings of the National Academy of Sciences, 1999