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

ABSTRACT: 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 ?S-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.

SUBMITTER: Moody IS

PROVIDER: S-EPMC3956296 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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

Moody Issa S IS Verde Shawn C SC Overstreet Cathie M CM Edward Robinson W W Weiss Gregory A GA

Bioorganic & medicinal chemistry letters 20120710 17

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 ...[more]

PMID: 22858140

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