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

摘要: PROTEIN tyrosine phosphatases (PTPases) and kinases coregulate the critical levels of phosphorylation necessary for intracellular signalling, cell growth differentiation1,2. Yersinia, causative bacteria bubonic plague other enteric diseases, secrete an active PTPase3, Yop51, that enters suppresses host immune cells4,5. Though catalytic domain is only ∼20% identical to human PTP1B6, Yersinia PTPase contains all invariant residues present in eukaryotic PTPases7, including nucleophilic Cys 403 which forms a phosphocysteine intermediate during catalysis3,8–10. We here structures unliganded (2.5 A resolution) tungstate-bound (2.6 A) crystal reveal positioned at centre distinctive phosphate-binding loop. This loop hub several hydrogen-bond arrays not stabilize bound oxyanion, but may activate as reactive thiolate. Binding tungstate triggers conformational change traps oxyanion swings Asp 356, important residue7, by ∼6 into site. The same anion-binding PTPases also found enzyme rhodanese11.