Crystal structure of Yersinia protein tyrosine phosphatase at 2.5 Å and the complex with tungstate

Abstract

PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth and differentiation^1,2. Yersinia, the causative bacteria of the bubonic plague and other enteric diseases, secrete an active PTPase³, Yop51, that enters and suppresses host immune cells^4,5. Though the catalytic domain is only ∼20% identical to human PTP1B⁶, the Yersinia PTPase contains all of the invariant residues present in eukaryotic PTPases⁷, including the nucleophilic Cys 403 which forms a phosphocysteine intermediate during catalysis^3,8–10. We present here structures of the unliganded (2.5 Å resolution) and tungstate-bound (2.6 Å) crystal forms which reveal that Cys 403 is positioned at the centre of a distinctive phosphate-binding loop. This loop is at the hub of several hydrogen-bond arrays that not only stabilize a bound oxyanion, but may activate Cys 403 as a reactive thiolate. Binding of tungstate triggers a conformational change that traps the oxyanion and swings Asp 356, an important catalytic residue⁷, by ∼6 Å into the active site. The same anion-binding loop in PTPases is also found in the enzyme rhodanese¹¹.