STRUCTURAL STUDIES OF ANESTHETIC BINDING SITE IN PROTEIN KINASE C (PKC)

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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. In the USA nearly 25 million patients/year undergo surgery using general anesthetics having very low therapeutic indices and whose molecular mechanisms remain unknown, hampering the design of improved agents. Anesthetics act at high concentrations, which has led to the assumption that the therapeutic binding events were nonspecific. Current views of the molecular mechanisms of anesthesia emphasize anesthetic-protein interactions. The molecular mechanism of general anesthesia remains poorly understood. Anesthetics are relatively nonspecific drugs that interact with transmembrane ion channels and soluble proteins, often causing unwanted side effects. Gaining a detailed understanding of the structural motifs governing anesthetic-protein interactions is a critical step in elucidating the molecular. The long-term objective of this project is to define the molecular determinants of those general anesthetic binding sites that effect the functions of proteins. A detailed understanding of the structural motifs governing protein-anesthetic interactions is a critical step in elucidating the molecular mechanisms underlying general anesthesia. Many of the targets of anesthetics are membrane proteins and difficult to study. However, recently protein kinase C (PKC), has been implicated as a target of anesthetics. We will use the subdomain C1B of PKC, to study the anestheic binding sites.