An electrospray ms-coupled microfluidic device for sub-second hydrogen/deuterium exchange pulse-labelling reveals allosteric effects in enzyme inhibition

Lab Chip. 2013 Jul 7;13(13):2528-32. doi: 10.1039/c3lc00007a. Epub 2013 Feb 21.

Abstract

In this work, we introduce an integrated, electrospray mass spectrometry-coupled microfluidic chip that supports the complete workflow for 'bottom up' hydrogen/deuterium exchange (HDX) pulse labelling experiments. HDX pulse labelling is used to measure structural changes in proteins that occur after the initiation of a reaction, most commonly folding. In the present case, we demonstrate the device on the β-lactamase enzyme TEM-1, identifying active site changes that occur upon acylation by a covalent inhibitor and subtle changes in conformational dynamics that occur away from the active site over a period of several second after the inhibitor is bound. Our results demonstrate the power of microfluidics-enabled sub-second HDX pulse labelling as a tool for studying allostery and show some intriguing correlations with mutagenesis studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Allosteric Regulation
  • Catalytic Domain
  • Deuterium / chemistry
  • Deuterium Exchange Measurement
  • Hydrogen / chemistry
  • Hydrogen Bonding
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods*
  • Spectrometry, Mass, Electrospray Ionization
  • beta-Lactamase Inhibitors
  • beta-Lactamases / metabolism*

Substances

  • beta-Lactamase Inhibitors
  • Hydrogen
  • Deuterium
  • beta-Lactamases
  • beta-lactamase TEM-1