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Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
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Metal induced structural changes observed in hexameric insulin.

R Sreekanth1, Vasantha Pattabhi, S S Rajan

  • 1Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, India.

International Journal of Biological Macromolecules
|November 4, 2008
PubMed
Summary
This summary is machine-generated.

Metal ions like manganese, rubidium, and nickel influence insulin hexamer structure. Different metal ions induce distinct conformational states, impacting insulin

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Protein Chemistry

Background:

  • Insulin hexamer structure is regulated by metal ions.
  • Conformational transitions (T to R states) are critical for insulin function.
  • Understanding metal ion coordination provides insights into insulin stability and activity.

Purpose of the Study:

  • To investigate the structural impact of different metal ions (Mn2+, Rb1+, Ni2+) on human arg-insulin.
  • To compare the resulting insulin hexamer conformations with the native Zn2+-bound state.
  • To elucidate the coordination chemistry of these metal ions within the insulin structure.

Main Methods:

  • X-ray crystallography was used to determine the structures of human arg-insulin bound to Mn2+, Rb1+, and Ni2+.
  • Comparative analysis of these structures with the known 2Zn2+ human arg-insulin structure.
  • Detailed examination of metal ion coordination environments.

Main Results:

  • 2Mn2+ and 1Rb1+ human arg-insulin adopted a T3R3f state, similar to 2Zn2+ insulin.
  • 4Ni2+ human arg-insulin adopted a T6 conformation.
  • Metal coordination was predominantly tetrahedral, except for nickel, which showed dual octahedral and tetrahedral coordination at one site.
  • Rubidium selectively occupied a high-affinity metal binding site.

Conclusions:

  • The type and coordination of metal ions significantly influence insulin hexamer conformation.
  • Distinct metal ions stabilize different structural states (T3R3f vs. T6).
  • These findings explain metal-induced structural changes and their implications for insulin.