April
21 , 2006 Cheryl
Arrowsmith (Ontario Cancer Institute, Banting
and Best Department of Medical Research & Department
of Medical Biophysics, University of Toronto) Structural Genomics Consortium
Structural
Genomics and Proteomics projects generate structures
of many uncharacterized proteins for which there
is no known function, as well as structures of "orphan"
members of protein gene families. Often the 3D structure
can provide strong clues to a biochemical function
that can be readily tested experimentally. Accidental
& intentional co-crystallization with small
molecules can also lead to functional hypotheses
or de-orphanization. Furthermore, these large scale
projects also purify many proteins for which structures
are not solved, but for which annotations are still
lacking. Therefore, in parallel with our structural
efforts we have also developed an array of catalytic
and biochemical screens that are applied to each
purified protein, whether or not its structure can
be determined. Strategies will be presented for
(1) rapid experimental confirmation of structure-based
hypotheses, (2) identification of functional ligands,
(3) identification of "practical ligands"
(ligands that bind and stabilize proteins for structure
determination) and (4) catalytic activities of un-or
under-characterized proteins.
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