Time-Resolved Ion Mobility-Mass Spectrometry Reveals Structural Transitions in the Disassembly of Modular Polyketide Syntheses.
Chunyi ZhaoSamuel T SlocumDavid H ShermanBrandon T RuotoloPublished in: Journal of the American Society for Mass Spectrometry (2024)
The type 1 polyketide synthase (PKS) assembly line uses its modular structure to produce polyketide natural products that form the basis of many pharmaceuticals. Currently, several cryoelectron microscopy (cryo-EM) structures of a multidomain PKS module have been constructed, but much remains to be learned. Here we utilize ion-mobility mass spectrometry (IM-MS) to record size and shape information and detect different conformational states of a 207 kDa didomain dimer comprised of ketosynthase (KS) and acyl transferase (AT), excised from full-length module. Furthermore, gas-phase stability differences between these different conformations are captured by collision induced unfolding (CIU) technology. Additionally, through tracking these forms as a function of time, we elucidate a detailed disassembly pathway for KS-AT dimers for the first time.
Keyphrases
- mass spectrometry
- high resolution
- liquid chromatography
- single molecule
- gas chromatography
- capillary electrophoresis
- high performance liquid chromatography
- high glucose
- molecular dynamics
- diabetic rats
- wastewater treatment
- molecular dynamics simulations
- high speed
- high throughput
- optical coherence tomography
- drug induced
- ms ms
- multiple sclerosis
- fatty acid
- oxidative stress
- healthcare
- single cell
- solid phase extraction