Structure and catalytic mechanism of human protein tyrosine phosphatome

Abstract

Together with protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs) serve as hallmarks in cellular signal transduction by controlling the reversible phosphorylation of their substrates. The human genome is estimated to encode more than 100 PTPs, which can be divided into eleven sub-groups according to their structural and functional characteristics. All the crystal structures of catalytic domains of sub-groups have been elucidated, enabling us to understand their precise catalytic mechanism and to compare their structures across all sub-groups. In this review, I describe the structure and mechanism of catalytic domains of PTPs in the structural context.

Fig. 1.. Classification of human protein tyrosine phosphatome. Figure is adapted from Alonso et al. .

Fig. 2.. Structure and mechanism of classical PTPs. (A) Ribbon diagram of TP1B (pdb code: 2HNP). (B) Crystal structure of PTP1B in complex with phosphor-Tyr (pdb code: 1PTV). Consensus sequences (HCX₅R), a general acid Asp181 and bound phosphor-Tyr are shown as stick models. (C) Twostep catalytic mechanism of classical PTP.

Fig. 3.. Crystal structures of representative Dusps. All Dusps are drawn with the same point of view. The secondary structural elements in blue indicate the deviations from canonical Dusp structure.

Fig. 4.. Structure and catalytic mechanism of eyes absent. (A) Ribbon diagram of catalytic domain of eyes absent. Catalytic domain (orange) and HBM (cyan) are colored differently. The active site aspartate and magnesium ion are drawn as ball-and-stick models. (B) Catalytic mechanism of eyes absent. A proposed two-step catalytic mechanism for eyes absent is shown.