Low-Molecular-Weight Protein Tyrosine Phosphatases

The eukaryotic low-molecular-weight protein tyrosine phosphatases (LMW PTPases) are cytoplasmic enzymes with molecular weights of approximately 18,000. This family of PTPases shares no sequence identity with the various high-molecular-weight (HMW) families except for the CXXXXXR signature sequence of the phosphate binding site. In the HMW PTPases, the conserved signature sequence, HCXAGXGR(S/T), is typically found in the C-terminal third of the protein, while in the LMW PTPases the related invariant motif XCXGNXCRS is found close to the N terminus. This motif forms the phosphate binding loop (P-loop). The P-loop peptide backbone in LMW PTPase has effectively the same structure as that found in a representative HMW PTPase from Yersinia, with Ca positions exhibiting only 0.37-A root mean square deviation. Thus, despite apparent differences in the consensus sequences, the phosphate binding regions of these proteins are surprisingly similar. Bovine liver and brain and human red cell, liver, and placenta enzymes were among the first to be extensively characterized.