Structure and Function of HIV-1 Integrase

HIV-1 integrase is a multidomain enzyme which is required for the integration of viral DNA into the host genome. It is one of three enzymes of HIV, the others being the Reverse Transcriptase and the Protease. It is an attractive target for therapeutic drug design. The enzyme consists of three domains. The N-terminal domain has a His2Cys2 motif which chelates zinc, the core domain has the catalytic DDE motif which is required for its enzymatic activity, and the C-terminal domain has an SH3-like fold which binds DNA nonspecifically. We review the structures of various integrase fragments, the core domain with inhibitors bound, and propose a model for DNA binding.