Structural insights into the homology and differences between mouse protein tyrosine phosphatase-sigma and human protein tyrosine phosphatase-sigma

Protein tyrosine phosphatases PTP-sigma （PTPo） plays an important role in the development of the nervous system and nerve regeneration. Although cumulative studies about the function of PTPo have been reported, yet limited data have been reported about the crystal structure and in vitro aetivity of mouse PTPcr. Here we report the crystal structure of mouse PTPcr tandem phos- phatase domains at 2.4 A, resolution. Then we compared the crystal structure of mouse PTPcr with human PTPcr and found that they are very similar, superimposing with a root mean square deviation of 0.45 A for 517 equivalent Ca atoms. But some residues in mouse PTPcr form loops while corresponding residues in human PTPcr form [3-sheets or o~-helices. Furthermore, we also compared in vitro activities of mouse PTPtr with human PTPcr and found that mouse PTPo has 25-fold higher specific activ- ity than human PTPcr does toward O-methyl fluorescein phosphate （OMFP） as the substrate. However, there is no significant activity difference between the mouse and the human enzyme detected with p-nitrophenylphosphate （pNPP） as the substrate. Mouse PTPo and human PTPa have different substrate specificities toward OMFP and pNPP as substrates. This work gives clues for further study of PTPa.