Conclusion

Prior to our study, many crystal structures of soluble Family I PPases from lower organisms are available. But no structural study on PPases from higher organisms has been reported. Given the emerging role of human PPA1 in tumorigenesis and the potential value of human PPA1 as a target for anti-cancer drug development, it becomes essential to obtain an atomic resolution structure of human PPA1. Such a structure is presented in the current study. The structure, in conjunction with results from modeling studies and previous knowledge on PPase structures, sheds new insights into the mechanism of PPA1 functions. The structure also provides the basis for structure-based drug discovery by using in silico virtual screening of small molecule compound libraries, which is being carried out in our lab.