"One of the major problems in trying to crystallize a protein is knowing whether it is really folded properly or has some disordered regions that might prevent crystallization," said Ian Wilson, DPhil., JCSG principal investigator, one of the PNAS authors and a professor of molecular biology and Skaggs Institute for Chemical Biology at TSRI. "So, no matter how pure the protein might be, it might never crystallize without some further modifications to make it more compact and ordered."
"We have used the information from DXMS to help guide our design efforts with protein targets that do not crystallize well," said another of the paper's authors, Scott Lesley, Ph.D., of the JCSG and the Genomics Institute of the Novartis Research Foundation. "Based on our experience to date, we have found that 20 to 40 percent of the targets that are amenable to crystallography could potentially benefit from the DXMS analysis. We think that DXMS analysis can be a key approach for salvaging problematic targets in structural genomics."
In the experiments reported in PNAS, Woods and his team of researchers used the DXMS technology with 24 proteins provided by JCSG, a research consortium funded by the National Institute of General Medical Sciences (NIGMS), to generate 3-dimensional structures of proteins. Within a two-week period, DXMS provided data and analysis for 21 of the proteins sufficient to localize unstructured regions in the proteins, information that typically takes months, if not years, to obtain.
Recent studies have shown that many, if not the majority of proteins contain some unstr
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Contact: Sue Pondrom
spondrom@ucsd.edu
619-543-6163
University of California - San Diego
15-Jan-2004