Evidence concerning insulin activity from the structure of a cross-linked derivative.
The important of crystallographic refinement for confident structural description, even at modest resolution, is demonstrated for N alpha A1,N epsilon B29-L,L-2,7-diaminosuberoyl (A2sb) insulin, a cross-linked insulin of low potency. The spatial arrangement of the cross-link itself can be described, and reliable estimates of the accuracy in atomic positions obtained. Comparison of invariant A2sb and native insulins shows a strong structural similarity, especially for the A chain surface residues and the dimer-forming residues of the B chain which have generally been strongly implicated in the receptor-binding region. Evidence from this analysis directs attention to the A chain, particularly the backbone, as being important in interactions with the membrane-bound receptor.
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003432:Cross-Linking Reagents; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000378:metabolism; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine
D003432:Cross-Linking Reagents; D007328:Insulin; C031688:insulin, 2,7-diaminosuberoyl, N(alpha)(A1), N(epsilon)(B29)-; D011972:Receptor, Insulin