This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bacterial transcription depends on a primary (group 1) [unreadable] that is essential for viability. In addition, most bacteria contain alternative [unreadable]'s that control regulons in response to environmental cues. Regulation of [unreadable] activity is a major mechanism by which bacteria respond to their environment. Many alternative [unreadable]'s are regulated by anti-[unreadable] factors. Despite the structural conservation of [unreadable]'s, anti-[unreadable]'s are structurally and functionally diverse, serving as the key response elements to sense and signal environmental cues to the core transcriptional apparatus via the alternative [unreadable]'s. In addition to modulation of [unreadable] function by cellular anti-[unreadable] factors, many bacteriophages have evolved ingenious mechanisms to inhibit and/or appropriate the host transcription apparatus. The primary [unreadable] ([unreadable]A) of the gram-positive pathogen Staphylococcus aureus (Sau) is targeted by phage proteins that inhibit bacterial growth. Phage G1 ORF67 was identified in a high-throughput screen as a transcriptional inhibitor that binds to the C-terminal domain (domain 4) of Sau [unreadable]A ([unreadable]A4). Our goal is to determine the co-crystal structure of G1 ORF67 with Sau [unreadable]A4, and to explore the functional mechanism through which ORF67 inhibits Sau transcription as well as it's role in phage G1 biology.