5J8R

Crystal Structure of the Catalytic Domain of Human Protein Tyrosine Phosphatase non-receptor Type 12 - K61R mutant

Summary for 5J8R

• Entry DOI: 10.2210/pdb5j8r/pdb
• Descriptor: Tyrosine-protein phosphatase non-receptor type 12 (2 entities in total)
• Functional Keywords: cancer, tyrosine phosphorylation, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q05209
• Total number of polymer chains: 4
• Total formula weight: 148185.00

Authors

Li, H.,Yang, F.,Xu, Y.F.,Wang, W.J.,Xiao, P.,Yu, X.,Sun, J.P. (deposition date: 2016-04-08, release date: 2016-04-27, Last modification date: 2023-11-08)

Primary citation

Li, H.,Yang, F.,Liu, C.,Xiao, P.,Xu, Y.F.,Liang, Z.L.,Liu, C.,Wang, H.M.,Wang, W.J.,Zheng, W.S.,Zhang, W.,Ma, X.Y.,He, D.F.,Song, X.Y.,Cui, F.A.,Xu, Z.G.,Yi, F.,Sun, J.P.,Yu, X.
Crystal structure and substrate specificity of PTPN12.
Cell Rep, 15:1-14, 2016

PubMed Abstract: PTPN12 is an important tumor suppressor that plays critical roles in various physiological processes. However, the molecular basis underlying the substrate specificity of PTPN12 remains uncertain. Here, enzymological and crystallographic studies have enabled us to identify two distinct structural features that are crucial determinants of PTPN12 substrate specificity: the pY+1 site binding pocket and specific basic charged residues along its surface loops. Key structurally plastic regions and specific residues in PTPN12 enabled recognition of different HER2 phosphorylation sites and regulated specific PTPN12 functions. In addition, the structure of PTPN12 revealed a CDK2 phosphorylation site in a specific PTPN12 loop. Taken together, our results not only provide the working mechanisms of PTPN12 for desphosphorylation of its substrates but will also help in designing specific inhibitors of PTPN12.

PubMed: 27134172
DOI: 10.1016/j.celrep.2016.04.016

Experimental method

X-RAY DIFFRACTION (2.043 Å)