1QZ0

Crystal Structure of the Yersinia Pestis Phosphatase YopH in Complex with a Phosphotyrosyl Mimetic-Containing Hexapeptide

Summary for 1QZ0

• Entry DOI: 10.2210/pdb1qz0/pdb
• Related PRD ID: PRD_000275
• Descriptor: Protein-tyrosine phosphatase yopH, ASP-ALA-ASP-GLU-FTY-LEU-NH2 (3 entities in total)
• Functional Keywords: phosphatase, ptpase, yoph, dephosphorylase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Yersinia pestis
• Total number of polymer chains: 6
• Total formula weight: 70454.61

Authors

Phan, J.,Lee, K.,Cherry, S.,Tropea, J.E.,Burke Jr, T.R.,Waugh, D.S. (deposition date: 2003-09-15, release date: 2003-11-25, Last modification date: 2024-10-30)

Primary citation

Phan, J.,Lee, K.,Cherry, S.,Tropea, J.E.,Burke Jr, T.R.,Waugh, D.S.
High-Resolution Structure of the Yersinia pestis Protein Tyrosine Phosphatase YopH in Complex with a Phosphotyrosyl Mimetic-Containing Hexapeptide
Biochemistry, 42:13113-13121, 2003

PubMed Abstract: 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.

PubMed: 14609321
DOI: 10.1021/bi030156m

Experimental method

X-RAY DIFFRACTION (1.5 Å)