In vitro evolution of an HIV integrase binding protein from a library of C-terminal domain γS-crystallin variants.

نویسندگان

  • Issa S Moody
  • Shawn C Verde
  • Cathie M Overstreet
  • W Edward Robinson
  • Gregory A Weiss
چکیده

A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystallin variant, termed integrase binding protein-10 (IBP-10), inhibits integrase catalysis with nanomolar K(i) values. IBP-10 interacts with the integrase C-terminal domain and inhibits integrase substrate affinity. This allosteric mechanism allows IBP-10 to inhibit drug-resistant integrase variants. The results demonstrate the applicability of the crystallin scaffold for the discovery of binding partners and enzyme inhibitors.

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عنوان ژورنال:
  • Bioorganic & medicinal chemistry letters

دوره 22 17  شماره 

صفحات  -

تاریخ انتشار 2012