1qz0
Crystal Structure of the Yersinia Pestis Phosphatase YopH in Complex with a Phosphotyrosyl Mimetic-Containing Hexapeptide
OverviewOverview
Yersinia pestis, the causative agent of bubonic plague, secretes a eukaryotic-like protein tyrosine phosphatase (PTPase) termed Yersinia outer protein H (YopH) that is essential for virulence. We have determined, for the first time, the crystal structure of the YopH PTPase domain in complex with a nonhydrolyzable substrate analogue, the hexapeptide mimetic Ac-DADE-F(2)Pmp-L-NH(2). As anticipated, the mode of ligand binding in the active site is similar to the way in which the corresponding phosphohexapeptide binds to the structurally homologous human PTP1B. Unexpectedly, however, the crystal structure also revealed a second substrate-binding site in YopH that is not present in PTP1B. The mode of binding and structural conformation of the hexapeptide analogue is quite different in the two sites. Although the biological function of the second substrate-binding site remains to be investigated, the structure of a substrate analogue in the active site of Y. pestis YopH opens the door for the structure-based design and optimization of therapeutic countermeasures to combat this potential agent of bioterrorism.
About this StructureAbout this Structure
1QZ0 is a Single protein structure of sequence from Yersinia pestis. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of the Yersinia pestis protein tyrosine phosphatase YopH in complex with a phosphotyrosyl mimetic-containing hexapeptide., Phan J, Lee K, Cherry S, Tropea JE, Burke TR Jr, Waugh DS, Biochemistry. 2003 Nov 18;42(45):13113-21. PMID:14609321 Page seeded by OCA on Sat May 3 06:52:27 2008