VISUALIZATION OF VACCINIA H1 DUAL-SPECIFICITY PHOSPHATASE WITH STAT1 PEPTIDE

Cornell University, Ithaca NY

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Abstract

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. Upon viral infection Vaccinia H1 (VH1) phosphatase immediately targets the host's immune response mechanism and disables it by dephosphorylating a signal transduction protein, STAT1. This is a shining example of how viruses evolved to survive under evolutionary pressure. VH1 is unique in that it can dephosphorylate both ser/thr and tyr residues, unlike other phosphatases that dephosphorylate one or the other. This class is called dual-specificity phosphatases (DSPs) of which VH1 is the prototype. Initial diffraction data was collected on our in-house xray generator to 1.95A. Similar crystals were taken to the CHESS beamline F1, where we were able to collect data past 1.3A. Both of these structures have been solved and refined( PDB ID: 2RF6 &3CEO). As the next step in this project, we would like to soak our crystals with a peptide derived from the transcription factor STAT1, which is thought to be a direct substrate of VH1. The STAT1 peptide has been designed to incorporate the region of STAT1 with the phosphotyrosine residue (701). We have soaked the crystals longer and co-crystallized VH1 with the peptide which should give stronger peaks of density.