CRYSTAL-STRUCTURE OF DESHEPTAPEPTIDE(B24-B30)INSULIN AT 1.6 ANGSTROM RESOLUTION - IMPLICATIONS FOR RECEPTOR-BINDING

The crystal structure of desheptapeptide (B24-B30) insulin (DHPI), a v irtually inactive analog of insulin, was determined at 1.6 Angstrom re solution, In the refined structure model, DHPI retains three alpha-hel ices (A1-A8, A12-A18, and B9-B19) as its structural framework, while g reat conformational changes occur in the N and C termini of B-chain, T he beta-turn, which lies in B20-B30 in insulin and insulin analogs wit h high potency, no longer exists in DHPI, Relative motion is observed among the three alpha-helices, each as a rigid functional group, In co ntrast, a region covering B5-B6 and A6-All exhibits a relatively stabl e conformation, We interpret our results as identifying: (i) the impor tance of beta-turn determining the receptor-binding potency of insulin and (ii) a leading role of Phe(B24) in maintaining the beta-turn stru cture.