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Chemistry and
Biochemistry
University of California
230 Physical Sciences Bldg.
Santa Cruz, CA 95064
Phone: (831) 459-4002
Fax: (831) 459-2935
Email
Maps & Directions
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Macromolecular
X-Ray Crystallography Facility
RESEARCH INTERESTS: We are trying to understand
RNA structure, catalysis and the origin of life.
RNA Structure
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Understanding the relationship between the three-dimensional
structure of a biological macromolecule and its function within an
organism is one of the most important and exciting open problems
residing at the interface between chemistry and biology. Employing
techniques from molecular biology as well as biophysical chemistry
(primarily static and time-resolved X-ray crystallography),
our primary
research objectives are to understand how structured RNAs can
have biological as well as enzymatic activity, and how proteins and
drugs interact with structured RNAs. Within that context, we also
encourage members of our laboratory to develop their own projects.
The nature of our research is fundamentally collaborative; we
collaborate with other research groups in the chemistry and biology
departments here and elsewhere. We aim to conduct our research in
an open, supportive and nonhierarchical environment, and to have
fun in doing so.
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Catalysis
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Since the discovery that RNA can be an enzyme, a fundamental
question has emerged: How does an RNA molecule fold up into a
precise three-dimensional structure capable of catalyzing a
chemical reaction? This problem is interesting not only from the
point of view of living organisms, but also in terms of trying to
understand how a pre-biotic RNA World populated by ribozymes, as
evolutionary precursors of today's protein enzymes found in all
living organisms, might have functioned. We have investigated this
question in the context of a number of catalytic RNAs, and have
focused upon the hammerhead
ribozyme. Our most recent structure reveals how tertiary
contacts within this ribozyme prime its active site for acid-base
catalysis.
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Origin of Life
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The RNA World hypothesis conjectures that pre-biotic
self-replicating molecules may have been RNAs. Of course no one
knows if life evolved from an RNA world, but it is possible to give
an experimental proof of principle if we can create
self-replicating RNAs in vitro. Our group is seeking to understand
what properties of ribozymes are of fundamental importance to a
plausible RNA World evolutionary scenario, and how RNA catalysts
evolve in three-dimensional space. As a first step, we have solved
the structure of an RNA Ligase
Ribozyme that catalyzes the assembly of RNA from
nucleotide-5'-triphosphate fragments as substrates.
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Current Projects
 We are working on
several sets of projects whose main theme is oriented toward trying
to understand the inter-relationships between macromolecular
structure and function. In the case of ribozymes, function includes
catalysis. We are primarily an X-ray crystallography lab, but we
are mainly interested in answering interesting biological
questions, and are therefore not wedded to a single technique.
Three recent projects are summarized on separate web pages:
SELECTED PUBLICATIONS
Complete publication
list
Recent
highlights
Michael P. Robertson and William G. Scott, The Structural Basis
of Ribozyme-Catalyzed RNA Assembly. Science 315: 1549-1553 (2007).
(reprint)
Monika Martick and William G. Scott, Tertiary Contacts Distant from
the Active Site Prime a Ribozyme for Catalysis. Cell 126: 309-320 (2006).
(reprint)
Anastasia J. Callaghan, Maria Jose Marcaida, Jonathan A. Stead,
Kenneth J. McDowall, William G. Scott and Ben F. Luisi, Structure
of E. coli RNase E catalytic domain and its implications for RNA
turnover and processing. Nature 437: 1187-1191 (2005).
(reprint)
M. P. Robertson, H. Igel, R. Baertsch, D. Haussler, M. Ares, Jr.,
and W. G. Scott, The Structure of a Rigorously Conserved RNA
Element within the SARS Virus Genome Public Library of Science: Biology
3(1): e5 (2004).
(reprint)
A. Szoke, W. G. Scott, J. Hajdu, Catalysis, evolution and
life. FEBS Letters
553: 18-20 (2003).
(reprint)
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