Crystal structure of desheptapeptide(B24-B30)insulin at 1.6 A resolution: implications for receptor binding.
The crystal structure of desheptapeptide (B24-B30) insulin (DHPI), a virtually inactive analog of insulin, was determined at 1.6 A resolution. In the refined structure model, DHPI retains three alpha-helices (A1-A8, A12-A18, and B9-B19) as its structural framework, while great conformational changes occur in the N and C termini of B-chain. The beta-turn, which lies in B20-B30 in insulin and insulin analogs with high potency, no longer exists in DHPI. Relative motion is observed among the three alpha-helices, each as a rigid functional group. In contrast, a region covering B5-B6 and A6-A11 exhibits a relatively stable conformation. We interpret our results as identifying: (i) the importance of beta-turn in determining the receptor-binding potency of insulin and (ii) a leading role of PheB24 in maintaining the beta-turn structure.
Bao
S J
SJ
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing.
Xie
D L
DL
Zhang
J P
JP
Chang
W R
WR
Liang
D C
DC
D018360:Crystallography, X-Ray; D007328:Insulin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
D007328:Insulin; D010446:Peptide Fragments; C061055:insulin, des(heptapeptide)(B24-B30)-