Metal Induced Conformational Changes in Human Insulin: Crystal Structures of Sr2+, Ni2+ and Cu2+ Complexes of Human Insulin
Abstract:Crystal structures of Sr2+, Ni2+ and Cu2+ of human insulin complexes have been determined. The structures of Sr2+ and Ni2+ complexes are similar to Zn2+ insulin and are in T6 conformation. (All the six monomers in the insulin hexamer are in Tensed conformation (T), which means the first eight residues of B-chain are in an extended conformation). Cu2+ complex, though it assumes T6 conformation, has more structural differences due to lowering of crystal symmetry and space group shift from H3 (Hexagonal crystal system) to P3 (Trigonal crystal system) and a doubling of the c axis. 2Ni2+ human insulin when compared to 4Ni2+ Arg insulin suggests that terminal modifications may be responsible for additional metal binding. All the three metals have been shown to have a role in diabetes and hence may be therapeutically useful.
Keywords: AN helix; Hexagonal crystal system; Insulin; Phe B-25; REFMAC; Relaxed conformation; SDS; Sr2+, Ni2+ and Cu2+ complexes; T3R3; Tensed conformation; Trigonal crystal system; X-ray crystallography; conformational state; metal binding; sodium dodecyl sulfate
Document Type: Research Article
Publication date: 2011-05-01
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