Hydrogen/Deuterium Exchange and Nuclear Magnetic Resonance Spectroscopy Reveal Dynamic Allostery on Multiple Time Scales in the Serine Protease Thrombin.

ABSTRACT: A deeper understanding of how hydrogen/deuterium exchange mass spectrometry (HDX-MS) reveals allostery is important because HDX-MS can reveal allostery in systems that are not amenable to nuclear magnetic resonance (NMR) spectroscopy. We were able to study thrombin and its complex with thrombomodulin, an allosteric regulator, by both HDX-MS and NMR. In this Perspective, we compare and contrast the results from both experiments and from molecular dynamics simulations. NMR detects changes in the chemical environment around the protein backbone N-H bond vectors, providing residue-level information about the conformational exchange between distinct states. HDX-MS detects changes in amide proton solvent accessibility and H-bonding. Taking advantage of NMR relaxation dispersion measurements of t

SUBMITTER: Peacock RB 

PROVIDER: S-EPMC9659328 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature