Structural insights into the homology and differences between mouse protein tyrosine phosphatase-sigma and human protein tyrosine phosphatase-sigma.
Protein tyrosine phosphatases PTP-sigma (PTPσ) plays an important role in the development of the nervous system and nerve regeneration. Although cumulative studies about the function of PTPσ have been reported, yet limited data have been reported about the crystal structure and in vitro activity of mouse PTPσ. Here we report the crystal structure of mouse PTPσ tandem phosphatase domains at 2.4 Å resolution. Then we compared the crystal structure of mouse PTPσ with human PTPσ and found that they are very similar, superimposing with a root mean square deviation of 0.45 Å for 517 equivalent Cα atoms. But some residues in mouse PTPσ form loops while corresponding residues in human PTPσ form β-sheets or α-helices. Furthermore, we also compared in vitro activities of mouse PTPσ with human PTPσ and found that mouse PTPσ has 25-fold higher specific activity than human PTPσ 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 PTPσ and human PTPσ have different substrate specificities toward OMFP and pNPP as substrates. This work gives clues for further study of PTPσ.
School of Life Science, East China Normal University, Shanghai, China.
Li
L
Hou
Jianchuan
J
Wang
Yueyang
Y
Zhou
Jingya
J
Li
Yi
Y
Zang
Jia
J
Li
D000595:Amino Acid Sequence; D000818:Animals; D003460:Crystallization / Q000379:methods*; D005452:Fluoresceins / Q000737:chemistry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D017434:Protein Structure, Tertiary; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity / Q000235:genetics
C032079:3-O-methylfluorescein phosphate; D005452:Fluoresceins; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C008644:nitrophenylphosphate; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2