Structural interpretation of reduced insulin activity as seen in the crystal structure of human Arg-insulin
Copyright policy )Structural interpretation of reduced insulin activity as seen in the crystal structure of human Arg-insulin
The N-terminal glycine of the A-chain in insulin is reported to be one of the residues that binds to the insulin receptor. Modifications near this region lead to variations in the biological activity of insulin. One such modification viz., an addition of an arginine at the N-terminal A-chain, was reported to possess two-thirds the activity of native insulin. The crystal structure of 2 zinc human arg (A0) insulin has been elucidated to 2A resolution to understand the mechanism of reduction in insulin activity. A conformational transition from T6 to T3R3(f) and a decrease in the surface accessibility of residues in the so called receptor binding region have been observed. The presence of arginine has also induced distortions in the A chain N-terminal helix. The subtle conformational alterations like decrease in surface accessibility, alterations in the charge surface and changes in the relative orientation of the two helices in the A chain may be responsible for the reduction in activity.
- University of Madras India
Models, Molecular, Zinc, Binding Sites, Protein Conformation, Surface Properties, Humans, Hypoglycemic Agents, Insulin, Arginine, Crystallography, X-Ray
Models, Molecular, Zinc, Binding Sites, Protein Conformation, Surface Properties, Humans, Hypoglycemic Agents, Insulin, Arginine, Crystallography, X-Ray
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