Acquisition of an X-Ray Area Detector

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ABSTRACT Acquisition of an X-ray Area Detector P.l. Robert J. Fletterick An area sensitive X-ray detector system is requested for X- ray crystallographic data collection for high resolution structure analyses of proteins. The new instrument is to augment the UCSF structural capability which is currently vastly oversubscribed. At present, persons typically wait in turn for one month to six weeks for time on one of the two existing area detectors. The new instrument requested is to overcome this rate limiting step in the structural science. The new phosphor storage technology used in the proposed detector system makes data collection more efficient and accurate. As structural analysis moves us to ask scientific questions using many mutations, or using modified inhibitors aimed at designing improved therapeutics, study of a single protein system can occupy as much as 50% of the time on one data collection instrument. Understanding the properties of mutant proteins or altered inhibitory compounds will require an analysis of structure as thoroughly as for the native proteins. The speed with which site-directed mutagenesis is accomplished requires rapid structural analysis for the scientist to remain close to the important scientific questions. In the following narrative, we list the projects of the three principal investigators and demonstrate the need for the new communal equipment. The laboratory to house the new machines will be renovated: a wall is to be added, plumbing changed, electrical installation and a safety enclosure will be built. The projects, most supported by NIH grants to the three P.I.s, are briefly described in narrative form, with references to published work where possible, and followed by a table. This lists the individual projects by title, the principal scientists working on the project and the status of the project. The status provides a brief summary of the current needs for data collection.