Hydrogen Exchange Mass Spectrometry: Principles and Capabilities.
Brier S, Engen JR.
In “Mass Spectrometry Analysis for Protein-Protein Interactions and Dynamics", 2008, In press.
Blackwell Publishing, Mark R. Chance, Editor.

CHAPTER 2
1. The chemistry of hydrogen exchange (HX)
   1.1. Principles of proton transfer
   1.2. Mechanisms of backbone amide hydrogen exchange
   1.3. Factors affecting hydrogen exchange
      1.3.1. pH effects
      1.3.2. Temperature effects
      1.3.3. Solvent and pressure effects
      1.3.4. Side-chain and ionic strength effects
2. HX mechanisms in proteins
3. Deuterium incorporation into proteins
   3.1. Continuous labeling
   3.2. Pulse labeling
   3.3. Other labeling strategies
4. Measuring HX with mass spectrometry (MS)
   4.1. Global versus local exchange
   4.2. Back-exchange
   4.3. Proteolysis before MS
   4.4. Mass measurements and data processing
5. Capabilities of HX MS in structural biology
   5.1. Protein folding studies
   5.2. Quality control
   5.3. Aid in structure elucidation
   5.4. Interactions & dynamics
6. Acknowledgements
7. References
8. Figure legends

ABSTRACT
Hydrogen exchange (HX) detected by mass spectrometry (MS) is an extremely valuable method for understanding proteins. The hydrogen exchange reaction itself, which has been understood by examining the exchange behavior of small amide models and peptide analogues, imposes specific limits on the overall HX MS method. In this chapter, the fundamental concepts that govern the hydrogen exchange reaction will be described. These concepts build a foundation for a discussion of basic HX MS methodology and its application to various biological problems. Examples of applying the method to specific problems will be provided in subsequent chapters of this book.

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Protein Analysis with Hydrogen-Deuterium Exchange Mass Spectrometry.
Mitchell JL, Engen JR.
Chapter 4 of “Mass Spectrometry Analysis of Proteins", Comprehensive Analytical Chemistry Series, Vol. 52, 83-102.
Elsevier, Julian Whitelegge, Editor.

1. Introduction
   1.1. Review of Protein Structure
   1.2. Obtaining information about conformation and dynamics
2. Experimental protocol
   2.1. Deuterium introduction
   2.2. Global versus local information
   2.3. HPLC and MS
   2.4. Data interpretation
3. Illustrative examples
   3.1. Protein conformation and the effects of mutation
   3.2. Binding interactions
   3.3. Investigating proteins lacking structural data
4. Conclusions

ABSTRACT
There are some properties of proteins that remain hidden to a mass spectrometer during simple molecular weight analyses. Some of these hidden protein properties include protein conformation, protein dynamics and protein interactions. How can these properties be revealed when mass spectrometers measure molecular weight not protein conformation? One way to uncover these properties with a mass spectrometer is to use a labeling method that “captures” the structural information before mass analysis occurs. The following chapter will describe one of these labeling methods: hydrogen-deuterium exchange. 

Mass Spectrometry Applications in Redox Biology.
Raza A, Engen JR.
In “Redox Biochemistry”, 2008.  Section 6.1, pp 228-237.
ISBN: 978-0-471-78625-5, John Wiley & Sons. Ruma Banerjee, Editor.

ABSTRACT Mass spectrometry is a technique that is used to identify and differentiate molecules on the basis of their mass.  Mass spectrometry has been called the universal detector because almost all types of molecules are amenable to analysis.  A few examples include determining adulteration of honey, detecting steroids in athletes, identifying unknown proteins, determining the post-translational modifications of protein, confirming mutations in proteins, quantitating drugs in biological matrices and measuring the concentration of pollutants in the air.  Depending on the application, mass spectrometers are usually coupled to a separation method, i.e. gas chromatography & mass spectrometry (GC-MS) or liquid chromatography & mass spectrometry (LC-MS).  In this section, the focus will be on LC-MS, which is the most useful technique for biological applications, and on the applications of mass spectrometry in redox biology.

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