Atomic coordinates for human phosphotyrosyl phosphatase activator (PTPA) and ATP.gamma.S bound by PTPA, as well as methods for using these atomic coordinates to prepare ATPase inhibitors of PTPA and ATPase inhibitors prepared using such methods are provided herein. Comprehensive biochemical analyses of the interactions of PTPA with ATP and protein phosphatase 2A are also provided. Compositions including mimetics and small molecules of the invention and, optionally, secondary agents may be used to treat disorders in which PTPA ATPase activity plays a contributing role.