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US researchers have exploited a new technique to identify almost all the chemical changes nature makes to human proteins by adding phosphate groups. They have now hooked up this data to the publicly accessible PhosphoMotif Finder in an effort to stimulate further biomedical research into the vital process of phosphorylation. Akhilesh Pandey of Johns Hopkins University and his colleagues used electron transfer dissociation (ETD) tandem mass spectrometry to identify protein fragments. The approach allows the fragments to retain their phosphorylated identity. Other spectrometric methods are "just too rough", Pandey explains, "We had to guess where they might be and nobody wants to chase false leads based on wrong guesses." The researchers have accumulated data on two decades' worth of research and compiled it into a searchable database. Details of the newly identified protein modifications were reported earlier this year in Proceedings of the National Academy of Sciences; they published a report on the databasing exercise in Nature Biotechnology. "Finding so many modifications at one time is a huge advance," Pandey says, "Phosphorylation is essential for controlling chemical reactions in our cells' protein factories, and phosphorylation gone awry has been implicated in several diseases. The ability to study more than one phosphorlyation at a time will help us understand some of these diseases - including cancers - sooner." The original aims of the research was merely to identify accurately as many protein modifications as possible, but in order to validate the results against published data they had to consolidate other researchers' work. "We went through and consolidated just about everything on phosphorylation that was out there," Pandey adds. The team analysed thousands of different proteins from human kidney cells and identified 1435 phosphorylations. When they checked back against twenty years of published data they found that about 4 out of every 5 phosphorylation had not been reported previously. With such a knowledge gap to fill, the team built an online search tool, PhosphoMotif Finder, which was incorporated into their Human Protein Reference Database. There are some 16000 phosphorylation sites in the database and anyone can use it to find a modified protein of interest. "The power of this technique is not just in the numbers," says Pandey, "Rather, we've found what you might call new information about old proteins, and we hope the new data will help researchers study their favourite proteins in greater depth." The team is now turning its attention to other protein modifications, with a similar goal in mind. Related links:
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