Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity

被引：37

作者：

Kelley, BS ^{[1
]}

Chang, LC ^{[1
]}

Bewley, CA ^{[1
]}

机构：

[1] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2002年 / 124卷 / 13期

关键词：

D O I：

10.1021/ja025537m

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The anti-HIV cyanobacterial protein cyanovirin-N can undergo domain swapping to form an intertwined dimer. The dimeric form is stable at low pH and millimolar concentrations. By deleting an amino acid from the hinge linker about which domain swapping occurs, we have constructed an obligate domain-swapped dimer of cyanovirin-N that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values. This obligate dimer displays enhanced anti-HIV activity relative to the wild-type cyanovirin-N monomer with an observed 3.5-fold decrease in IC50 (9nM for the dimer vs 32 nM for the monomer) for inhibition of HIV-1 envelope-mediated cell fusion and, when expressed in Escherichia coli, can be rapidly obtained in >98% purity in a single chromatographic step.

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页码：3210 / 3211

页数：2

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