X-ray crystallographic and hydrogen deuterium exchange studies confirm alternate kinetic models for homolog insulin monomers.

ABSTRACT: Despite the crucial role of various insulin analogs in achieving satisfactory glycemic control, a comprehensive understanding of their in-solution dynamic mechanisms still holds the potential to further optimize rapid insulin analogs, thus significantly improving the well-being of individuals with Type 1 Diabetes. Here, we employed hydrogen-deuterium exchange mass spectrometry to decipher the molecular dynamics of newly modified and functional insulin analog. A comparative analysis of H/D dynamics demonstrated that the modified insulin exchanges deuterium atoms faster and more extensively than the intact insulin aspart. Additionally, we present new insights derived from our 2.5 Å resolution X-ray crystal structure of modified hexamer insulin analog at ambient temperature. Furthermore, we o

SUBMITTER: Ayan E 

PROVIDER: S-EPMC12011231 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature