; R o o t E n t r y F #2 > @ C o m p O b j b W o r d D o c u m e n t O b j e c t P o o l #2 > #2 > 4 @ C D E F G H I J K L F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; 9505977 Kohlstaedt To learn how dimer formation differs in the closely related polymerases, the Kohlstaedt lab will crystallize Maloney murine leukemia virus and avian sarcoma virus reverse transcriptases . Stucture solutions will be supplemented by biochemical experiments aimed at delineating domain boundaries and domain functions in all three of these polymerases. Collaborative projects extend the training potential of Dr. Kohlstaedt's research plan. Plans are being executed that will lead to the solving of other crystal structures with participation of students from other research groups. These students will learn to think critically about structural problems, and some will participate in the solving of crystal structures. Besides the training aspect of her research plan, which involves graduate and undergraduate students and will later involve postdoctoral trainees, Dr. Kohlstaedt will be actively involved in improving formal instruction in structural biology and biophysics. She will be involved in initiating new course offerings and updating existing ones. New courses proposed include "Macrom olecular Crystallography" to be offered to both graduates and undergraduates and "physical chemistry for biochemistry" to be part of the required curriculum for undergraduate biochemistry majors. Two extant courses will be modernized: "Protein Chemistry" and "Biophysical Chemistry," both graduate courses. In addition, Dr. Kohlstaedt will offer literature review and tutorial classes in structural biology. %%% The ultimate goal of our research is to understand structure-function relationships in enzymes. Viral polymerases offer ~n ideal model system for the pursuit of this goal since they seem to represent multiple, convergent solutions to the same problems of binding and catalysis. We currently are working to grow crystals of adenovirus polymerase and of ASV and MuLV reverse transcriptases. Our overall approach is to study the structures of viral polymerases by both crystallography and biochemistry. By these complimentary techniques we hope to build a detailed knowledge of the structure and function of these enzymes. Our goals for the proposed period of support are: 1. Biochemical definition of domain boundaries in adenovirus polymerase and identification of the domain(s) that function in the initiation of genome replication. 2. Physical definition of the polymerization state of MuLV reverse transcriptase in the presence of DNA. 3. Growth of crystals suitable for xray structure analysis of adenovirus polymerase, a fragment of the polymerase, adenovirus terminal protein, the host factor NF-1 and/or binary complexes between these proteins. 4. Growth of crystals suitable for x-ray structure analysis of ASV and/or MuLV reverse transcriptase. These experiments approach two goals: The first is a better understanding of the entire replication particle in adenovirus. The second is a better understanding of protein folding and dimerization in lentiviral reverse transcriptases. *** @ ....()()))()() ; Oh +' 0 $ H l D h R:WWUSERTEMPLATENORMAL.DOT jack cohen Rhonda Young @ { 9 @ M S u m m a r y I n f o r m a t i o n ( B > @ Zy> @ 2~ Microsoft Word 6.0 3 e = e C x z z z

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
Application #
Program Officer
David A. Rockcliffe
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Project End
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University of California Santa Barbara
Santa Barbara
United States
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