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 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.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GAdoi
10.1016/j.bmcl.2012.07.008subject
Has Abstractpub_date
2012-09-01 00:00:00pages
5584-9issue
17eissn
0960-894Xissn
1464-3405pii
S0960-894X(12)00875-Xjournal_volume
22pub_type
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