Insights into enzyme structure and dynamics elucidated by amide H/D exchange mass spectrometry.
Conformational changes and protein dynamics play an important role in the catalytic efficiency of enzymes. Amide H/D exchange mass spectrometry (H/D exchange MS) is emerging as an efficient technique to study the local and global changes in protein structure and dynamics due to ligand binding, protein activation-inactivation by modification, and protein-protein interactions. By monitoring the selective exchange of hydrogen for deuterium along a peptide backbone, this sensitive technique probes protein motions and structural elements that may be relevant to allostery and function. In this report, several applications of H/D exchange MS are presented which demonstrate the unique capability of amide hydrogen/deuterium exchange mass spectrometry for examining dynamic and structural changes associated with enzyme catalysis.
Busenlehner
Laura S
LS
Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0416, USA. laura.busenlehner@vanderbilt.edu
Armstrong
Richard N
RN
D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003903:Deuterium / Q000737:chemistry*; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D005544:Forecasting; D006859:Hydrogen / Q000737:chemistry*; D008024:Ligands; D013058:Mass Spectrometry / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity
D000577:Amides; D004798:Enzymes; D008024:Ligands; D010455:Peptides; D021122:Protein Subunits; D011506:Proteins; D006859:Hydrogen; D003903:Deuterium