Metal Induced Conformational Changes in Human Insulin: Crystal Structures of Sr2+, Ni2+ and Cu2+ Complexes of Human Insulin

Nagampalli      Raghavendra Sashi Krishna; Vasantha      Pattabhi; S.      S. Rajan

doi:10.2174/092986611794927929

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: Insulin, X-ray crystallography, conformational state, metal binding, Sr2+, Ni2+ and Cu2+ complexes, Hexagonal crystal system, Trigonal crystal system, SDS, sodium dodecyl sulfate, AN helix, Tensed conformation, Relaxed conformation, T3R3, REFMAC, Phe B-25Insulin, X-ray crystallography, conformational state, metal binding, Sr2+, Ni2+ and Cu2+ complexes, Hexagonal crystal system, Trigonal crystal system, SDS, sodium dodecyl sulfate, AN helix, Tensed conformation, Relaxed conformation, T3R3, REFMAC, Phe B-25