This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have collected data and determined the structures of several macromolecules that are important in various ways to human health. We determined the structure of Nep1, a pseudouridine methyltransferase responsible for methylation of the hypermodified base near the decoding region of the ribosome's small subunit, bound to substrate analog RNA. We therefore provide a structural basis for catalytic activity and specificity. Nep1 is also the site of a mutation that cause Bowen-Conradi Syndrome in humans, a rare genetic disease resulting ultimately in childhood lethality.
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