This protein was insoluble, potentially due to unfavorable interactions involving the hydrophobic sidechain of Val176. The corresponding residue in native PTP1B is Tyr176, whose hydroxyl group forms a hydrogen bond with the sidechain of Ser190. Val176 was restored to Tyr as is native in PTP1B, yielding Chimera 1, which was soluble but inactive. Some of the subsequent chimeras were insoluble, for reasons that are not evident, and were not characterized. Chimeras 3, 4 and 7